LUCIFER: a Multi-Mode NIR Instrument for the LBT - Seifert, Walter; Appenzeller, Immo; Baumeister, Harald; Bizenberger, Peter; Bomans, Dominik; Dettmar, Ralf-Juergen; Grimm, Bernard; Herbst, Tom; Hofmann, Reiner; Juette, Marcus; Laun, Werner; Lehmitz, Michael; et al. (2002)

LUCIFER status report, summer 2004 - Mandel, Holger; Appenzeller, Immo; Seifert, Walter; Baumeister, Harald; Bizenberger, Peter; Dettmar, Ralf-Juergen; Gemperlein, Hans; Grimm, Bernhard; Herbst, Tom M.; Hofmann, Reiner; Jutte, Marcus; Laun, Werner; et al. (2004)

The cryogenic MOS unit for LUCIFER - Hofmann, Reiner; Gemperlein, Hans; Grimm, Bernhard; Jutte, Marcus; Mandel, Holger; Polsterer, Kai; Weisz, Harald (2004)

The development process of the LUCIFER control software - Juette, Marcus; Polsterer, Kai L.; Lehmitz, Michael; Knierim, Volker (2004)

LUCIFER status report: Summer 2006 - Mandel, H. G.; Appenzeller, I.; Seifert, W.; Baumeister, H.; Dettmar, R.-J.; Feiz, C.; Gemperlein, H.; Germeroth, A.; Grimm, B.; Heidt, J.; Herbst, T.; Hofmann, R.; et al. (2006)

Lucifer VR: a virtual instrument for the LBT - Polsterer, Kai L.; Jütte, Marcus; Knierim, Volker; Lehmitz, Michael; Mandel, Holger (2006)

The Java based control software of the LUCIFER instrument - Jütte, Marcus; Polsterer, Kai; Knierim, Volker; Luks, Thomas; Schimmelmann, Jan; Muhlack, Tobias; Mandel, Holger; Lehmitz, Michael (2006)

User interaction with the LUCIFER control software - Knierim, Volker; Jütte, Marcus; Polsterer, Kai; Schimmelmann, Jan (2006)

LUCIFER status report: summer 2008 - Mandel, Holger; Seifert, Walter; Hofmann, Reiner; Jütte, Marcus; Lenzen, Rainer; Ageorges, Nancy; Bomans, Dominik; Buschkamp, Peter; Dettmar, Ralf-Jürgen; Feiz, Carmen; Gemperlein, Hans; Germeroth, André; et al. (2008)

LUCIFER1 commissioning at the LBT - Ageorges, N.; Seifert, W.; Jütte, M.; Knierim, V.; Lehmitz, M.; Germeroth, A.; Buschkamp, P.; Polsterer, K.; Pasquali, A.; Naranjo, V.; Gemperlein, H.; Hill, J.; et al. (2010)

The LUCIFER MOS: a full cryogenic mask handling unit for a near-infrared multi-object spectrograph - Buschkamp, Peter; Hofmann, Reiner; Gemperlein, Hans; Polsterer, Kai; Ageorges, Nancy; Eisenhauer, Frank; Lederer, Reinhard; Honsberg, Mathias; Haug, Marcus; Eibl, Johann; Seifert, Walter; Genzel, Reinhard (2010)

LUCIFER1: performance results - Seifert, Walter; Ageorges, Nancy; Lehmitz, Michael; Buschkamp, Peter; Knierim, Volker; Polsterer, Kai; Germeroth, Andre; Pasquali, Anna; Naranjo, Vianak; Jütte, Marcus; Feiz, Carmen; Gemperlein, Hans; et al. (2010)

The LUCIFER control software - Jütte, Marcus; Knierim, Volker; Polsterer, Kai; Lehmitz, Michael; Storz, Clemens; Seifert, Walter; Ageorges, Nancy (2010)

Photometric Redshift Estimation of Quasars: Local versus Global Regression - Gieseke, F.; Polsterer, Kai; Zinn, Peter-Christian (Astronomical Data Analysis Software and Systems XXI, 2012)
The task of estimating an object's redshift based on photometric data is one of the most important ones in astronomy. This is especially the case for quasars. Common approaches for this regression task are based on nearest neighbor search, template fitting schemes, or combinations of, e.g., clustering and regression techniques. As we show in this work, simple frameworks like k-nearest neighbor regression work extremely well if one considers the overall feature space (containing patterns of all objects with low, middle, and high redshifts). However, such methods naturally fail as soon as only very few or even no training patterns are given in the appropriate region of the feature space. In the literature, a wide range of other regression techniques can be found. Among the most popular ones are regularized regression schemes like ridge regression or support vector regression. In this work, we show that an out-of-the-box application of this type of schemes for the whole feature space is difficult due to the involved computational requirements and the specific properties of the data at hand. However, in contrast to nearest neighbor search schemes, such methods can be employed to extrapolate, i.e., they can be used to predict redshifts for patterns in new, unseen regions of the feature space.

Approximate variational inference based on a finite sample of Gaussian latent variables - Gianniotis, Nikos; Schnörr, Christoph; Molkenthin, Christian; Bora, Sanjay Singh (Pattern Anal Applic, 2016)

Model-coupled autoencoder for time series visualisation - Gianniotis, Nikolaos; Kügler, Sven D.; Tiňo, Peter; Polsterer, Kai L. (Neurocomputing, 2016)

A spectral model for multimodal redshift estimation - Kugler, Sven D.; Gianniotis, Nikolaos; Polsterer, Kai L. (2016 IEEE Symposium Series on Computational Intelligence (SSCI), 2016)

Optical continuum photometric reverberation mapping of the Seyfert-1 galaxy Mrk509 - Nuñez, F Pozo; Gianniotis, Nikos; Blex, J; Lisow, T; Chini, R; Polsterer, Kai; Pott, J-U; Esser, J; Pietrzyński, G (Monthly Notices of the Royal Astronomical Society, 2019)

Efficient Optimization of Echo State Networks for Time Series Datasets - Maat, Jacob Reinier; Gianniotis, Nikos; Protopapas, Pavlos (2018 International Joint Conference on Neural Networks (IJCNN), 2018)

Empirical Analysis of Phylogenetic Quasi-Terraces - Breitling, Paula; Stamatakis, Alexandros; Chernomor, Olga; Bettisworth, Ben; Reszczynski, Lukasz (bioRxiv, 2019)
Terraces in phylogenetic tree space are, among other things, important for the design of tree space search strategies. While the phenomenon of phylogenetic terraces is already known for unlinked partition models on partitioned phylogenomic data sets, it has not yet been studied if an analogous structure is present under linked and scaled partition models. To this end, we analyze aspects such as the log-likelihood distributions, likelihood-based significance tests, and nearest neighborhood interchanges on the trees residing on a terrace and compare their distributions among unlinked, linked, and scaled partition models. Our study shows that there exists a terrace-like structure under linked and scaled partition models as well. We denote this phenomenon as quasi-terrace. Therefore quasi-terraces should be taken into account in the design of tree search algorithms as well as when reporting results on ‘the’ final tree topology in empirical phylogenetic studies.

Treerecs: an integrated phylogenetic tool, from sequences to reconciliations - Comte, Nicolas; Morel, Benoit; Hasic, Damir; Guéguen, Laurent; Boussau, Bastien; Daubin, Vincent; Penel, Simon; Scornavacca, Celine; Gouy, Manolo; Stamatakis, Alexandros; Tannier, Eric; Parsons, David P. (bioRxiv, 2019)
Motivation Gene and species tree reconciliation methods can be used to root gene trees and correct uncertainties that are due to scarcity of signal in multiple sequence alignments. So far, reconciliation tools have not been integrated in standard phylogenetic software and they either lack of performance on certain functions, or usability for biologists.

ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models - Darriba, Diego; Posada, David; Kozlov, Alexey; Stamatakis, Alexandros; Morel, Benoit; Flouri, Tomas (Molecular Biology and Evolution, 2019)
ModelTest-NG is a reimplementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one to two orders of magnitude faster than jModelTest and ProtTest but equally accurate and introduces several new features, such as ascertainment bias correction, mixture, and free-rate models, or the automatic processing of single partitions. ModelTest-NG is available under a GNU GPL3 license at https://github.com/ddarriba/modeltest , last accessed September 2, 2019.

Long metabarcoding of the eukaryotic rDNA operon to phylogenetically and taxonomically resolve environmental diversity - Jamy, Mahwash; Foster, Rachel; Barbera, Pierre; Czech, Lucas; Kozlov, Alexey; Stamatakis, Alexandros; Baß, David; Burki, Fabien (Molecular Ecology Resources, 2019)
High-throughput environmental DNA metabarcoding has revolutionized the analysis of microbial diversity, but this approach is generally restricted to amplicon sizes below 500 base pairs. These short regions contain limited phylogenetic signal, which makes it impractical to use environmental DNA in full phylogenetic inferences. However, new long-read sequencing technologies such as the Pacific Biosciences platform may provide sufficiently large sequence lengths to overcome the poor phylogenetic resolution of short amplicons. To test this idea, we amplified soil DNA and used PacBio Circular Consensus Sequencing (CCS) to obtain a ~4500 bp region of the eukaryotic rDNA operon spanning most of the small (18S) and large subunit (28S) ribosomal RNA genes. The CCS reads were first treated with a novel curation workflow that generated 650 high-quality OTUs containing the physically linked 18S and 28S regions of the long amplicons. In order to assign taxonomy to these OTUs, we developed a phylogeny-aware approach based on the 18S region that showed greater accuracy and sensitivity than similarity-based and phylogenetic placement-based methods using shorter reads. The taxonomically-annotated OTUs were then combined with available 18S and 28S reference sequences to infer a well-resolved phylogeny spanning all major groups of eukaryotes, allowing to accurately derive the evolutionary origin of environmental diversity. A total of 1019 sequences were included, of which a majority (58%) corresponded to the new long environmental CCS reads. Comparisons to the 18S-only region of our amplicons revealed that the combined 18S-28S genes globally increased the phylogenetic resolution, recovering specific groupings otherwise missing. The long-reads also allowed to directly investigate the relationships among environmental sequences themselves, which represents a key advantage over the placement of short reads on a reference phylogeny. Altogether, our results show that long amplicons can be treated in a full phylogenetic framework to provide greater taxonomic resolution and a robust evolutionary perspective to environmental DNA.

Genesis and Gappa: Processing, Analyzing and Visualizing Phylogenetic (Placement) Data - Czech, Lucas; Barbera, Pierre; Stamatakis, Alexandros (bioRxiv, 2019)
The ever increasing amount of genomic and meta-genomic sequence data has transformed biology into a data-driven and compute-intensive discipline. Hence, there is a need for efficient algorithms and scalable implementations thereof for analysing such data.

12 Grand Challenges in Single-Cell Data Science - Laehnemann, David; Köster, Johannes; Szczurek, Ewa; McCarthy, Davis J; Hicks, Stephanie C; Robinson, Mark D; Vallejos, Catalina A; Beerenwinkel, Niko; Campbell, Kieran R; Mahfouz, Ahmed; Pinello, Luca; Skums, Pavel; et al. (PeerJ, 2019)

GeneRax: A tool for species tree-aware maximum likelihood based gene tree inference under gene duplication, transfer, and loss - Morel, Benoit; Kozlov, Alexey; Stamatakis, Alexandros; Szöllősi, Gergely J. (bioRxiv, 2019)
Inferring gene trees is difficult because alignments are often too short, and thus contain insufficient signal, while substitution models inevitably fail to capture the complexity of the evolutionary processes. To overcome these challenges species tree-aware methods seek to use information from a putative species tree. However, there are few methods available that implement a full likelihood framework or account for horizontal gene transfers. Furthermore, these methods often require expensive data pre-processing (e.g., computing bootstrap trees), and rely on approximations and heuristics that limit the exploration of tree space. Here we present GeneRax, the first maximum likelihood species tree-aware gene tree inference software. It simultaneously accounts for substitutions at the sequence level and gene level events, such as duplication, transfer and loss and uses established maximum likelihood optimization algorithms. GeneRax can infer rooted gene trees for an arbitrary number of gene families, directly from the per-gene sequence alignments and a rooted, but undated, species tree. We show that compared to competing tools, on simulated data GeneRax infers trees that are the closest to the true tree in 90% of the simulations in terms relative Robinson-Foulds distance. While, on empirical datasets, GeneRax is the fastest among all tested methods when starting from aligned sequences, and that it infers trees with the highest likelihood score, based on our model. GeneRax completed tree inferences and reconciliations for 1099 Cyanobacteria families in eight minutes on 512 CPU cores. Thus, its advanced parallelization scheme enables large-scale analyses. GeneRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax.

Modeling Structural Constraints on Protein Evolution via Side-Chain Conformational States - Perron, Umberto; Kozlov, Alexey; Stamatakis, Alexandros; Goldman, Nick; Moal, Iain H (Molecular Biology and Evolution, 2019)
Few models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well as information about the rotamer configuration of its side-chain: the discrete geometric pattern of permitted side-chain atomic positions, as defined by the dihedral angles between covalently linked atoms. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state “Dayhoff-like” model that shows that the evolutionary properties of amino acids depend strongly upon side-chain geometry. The model performs as well as or better than traditional 20-state models for divergence time estimation, tree inference, and ancestral state reconstruction. We conclude that not only is rotamer configuration a valuable source of information for phylogenetic studies, but that modeling the concomitant evolution of sequence and structure may have important implications for understanding protein folding and function.

LUCIFER control software: an OO approach using CORBA technology - Jütte, Marcus; Polsterer, Kai L.; Lehmitz, Michael; Dettmar, Ralf-Jürgen (2002)
In this paper we present the design of the control software for the LBT NIR spectroscopic Utility with Camera and Integral- Field Unit for Extragalactic Research (LUCIFER) which is one of the first-light instruments for the Large Bin-ocular Telescope (LBT) on Mt. Graham, Arizona. The LBT will be equipped with two identical LUCIFER instruments for both mirrors. Furthermore we give an overview of the intended hardware structure of the instrument. Since the project requires a detailed and exact modeling of the software we present UML diagrams starting with an overall model down to use case, activity and class diagrams including an example for one special instrument unit.

Mixed Variational Inference - Gianniotis, Nikos (2019)
The Laplace approximation has been one of the workhorses of Bayesian inference. It often delivers good approximations in practice despite the fact that it does not strictly take into account where the volume of posterior density lies. Variational approaches avoid this issue by explicitly minimising the Kullback-Leibler divergence DKL between a postulated posterior and the true (unnormalised) logarithmic posterior. However, they rely on a closed form DKL in order to update the variational parameters. To address this, stochastic versions of variational inference have been devised that approximate the intractable DKL with a Monte Carlo average. This approximation allows calculating gradients with respect to the variational parameters. However, variational methods often postulate a factorised Gaussian approximating posterior. In doing so, they sacrifice a-posteriori correlations. In this work, we propose a method that combines the Laplace approximation with the variational approach. The advantages are that we maintain: applicability on non-conjugate models, posterior correlations and a reduced number of free variational parameters. Numerical experiments demonstrate improvement over the Laplace approximation and variational inference with factorised Gaussian posteriors.

Specifications of Standards in Systems and Synthetic Biology - Schreiber, Falk; Bader, Gary D.; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan (Journal of Integrative Bioinformatics, 2015)

Data Management in Computational Systems Biology: Exploring Standards, Tools, Databases, and Packaging Best Practices - Stanford, Natalie J.; Scharm, Martin; Dobson, Paul D.; Golebiewski, Martin; Hucka, Michael; Kothamachu, Varun B.; Nickerson, David; Owen, Stuart; Pahle, Jürgen; Wittig, Ulrike; Waltemath, Dagmar; Goble, Carole; et al. (Yeast Systems Biology, 2019)

Conceptual Framework of Organic Electronics - Gryn'ova, Ganna; Corminboeuf, Clémence (CHIMIA International Journal for Chemistry, 2019)
In this account, we discuss the common molecular features and the related chemistry concepts across several different areas of organic electronics, including molecular semiconductors and single-molecule junctions. Despite seemingly diverse charge transport mechanisms and device set-ups, various molecular electronics systems can benefit from the same fundamental principles of physical organic chemistry, based upon the electronic structure and geometry of their molecular building blocks and the intermolecular interactions between them. This is not an exhaustive review of organic electronics, but rather a focused account of primarily our own recent efforts aimed at developing a unified approach to understanding and designing conductive molecular species for diverse electronic applications.

Topology-Driven Single-Molecule Conductance of Carbon Nanothreads - Gryn'ova, Ganna; Corminboeuf, Clémence (The Journal of Physical Chemistry Letters, 2019)
Highly conductive single-molecule junctions typically involve π-conjugated molecular bridges, whose frontier molecular orbital energy levels can be fine-tuned to best match the Fermi level of the leads. Fully saturated wires, e.g., alkanes, are typically thought of as insulating rather than highly conductive. However, in this work, we demonstrate in silico that significant zero-bias conductance can be achieved in such systems by means of topology. Specifically, caged saturated hydrocarbons offering multiple σ-conductance channels afford transmission far beyond what could be expected based upon conventional superposition laws, particularly if these pathways are composed entirely from quaternary carbon atoms. Computed conductance of molecular bridges based on carbon nanothreads, e.g., polytwistane, is not only of appreciable magnitude; it also shows a very slow decay with increasing nanogap, similarly to the case of π-conjugated wires. These findings offer a way to manipulate the transport properties of molecular systems by means of their topology, alternatively to the traditionally invoked electronic structure.

Experimental Evidence for Long-Range Stabilizing and Destabilizing Interactions between Charge and Radical Sites in Distonic Ions - Marshall, David L.; Gryn'ova, Ganna; Poad, Berwyck L.J.; Bottle, Steven E.; Trevitt, Adam J.; Coote, Michelle L.; Blanksby, Stephen J. (International Journal of Mass Spectrometry, 2019)
Polarizable radical sites in distonic radical anions are stabilized by ostensibly remote negative charges. Computational evidence suggests bond dissociation energies of closed-shell precursors are significantly lowered by through-space interactions with a proximate negative charge, however direct experimental confirmation has proved challenging. Herein, we exploit two complementary tandem mass spectrometry strategies to probe the influence of a remote charge on the stability of nitroxyl radicals, and vice versa. Dissociation of negatively charge-tagged alkoxyamines reveals that the energetic onset of radical formation is dependent on the proximity and basicity of the charged group, thus providing direct evidence for a charge-induced stabilization of the nitroxyl radical. Complementary kinetic method experiments on a series of proton-bound dimers demonstrate that the presence of a nitroxyl radical decreases the proton affinity for a selection of proximate ionic groups. These data show excellent agreement with quantum-chemical calculations and provide a general framework to explore the magnitude and direction of charge-radical interactions through systematic exploration of the identity, polarity and the proximity of the ion to the radical site. These findings expand our fundamental understanding of radical ion energetics that underpin the application of distonic ions as models for neutral radical reactivity, and open new avenues for exploiting these interactions as chemical switches.

Read between the Molecules: Computational Insights into Organic Semiconductors - Gryn'ova, Ganna; Lin, Kun-Han; Corminboeuf, Clémence (Journal of the American Chemical Society, 2018)
The performance and key electronic properties of molecular organic semiconductors are dictated by the interplay between the chemistry of the molecular core and the intermolecular factors of which manipulation has inspired both experimentalists and theorists. This Perspective presents major computational challenges and modern methodological strategies to advance the field. The discussion ranges from insights and design principles at the quantum chemical level, in-depth atomistic modeling based on multiscale protocols, morphological prediction and characterization as well as energy-property maps involving data-driven analysis. A personal overview of the past achievements and future direction is also provided.

Noncovalent Molecular Electronics - Gryn'ova, Ganna; Corminboeuf, C. (The Journal of Physical Chemistry Letters, 2018)
Molecular electronics covers several distinctly different conducting architectures, including organic semiconductors and single-molecule junctions. The noncovalent interactions, abundant in the former, are also often found in the latter, i.e., the dimer junctions. In the present work, we draw the parallel between the two types of noncovalent molecular electronics for a range of π-conjugated heteroaromatic molecules. In silico modeling allows us to distill the factors that arise from the chemical nature of their building blocks and from their mutual arrangement. We find that the same compounds are consistently the worst and the best performers in the two types of electronic assemblies, emphasizing the universal imprint of the underlying chemistry of the molecular cores on their diverse charge transport characteristics. The interplay between molecular and intermolecular factors creates a spectrum of noncovalent conductive architectures, which can be manipulated using the design strategies based upon the established relationships between chemistry and transport.

Steric “Attraction”: Not by Dispersion Alone - Gryn'ova, Ganna; Corminboeuf, Clémence (Beilstein Journal of Organic Chemistry, 2018)
Non-covalent interactions between neutral, sterically hindered organic molecules generally involve a strong stabilizing contribution from dispersion forces that in many systems turns the ‘steric repulsion’ into a ‘steric attraction’. In addition to London dispersion, such systems benefit from electrostatic stabilization, which arises from a short-range effect of charge penetration and gets bigger with increasing steric bulk. In the present work, we quantify this contribution for a diverse set of molecular cores, ranging from unsubstituted benzene and cyclohexane to their derivatives carrying tert-butyl, phenyl, cyclohexyl and adamantyl substituents. While the importance of electrostatic interactions in the dimers of sp2-rich (e.g., π-conjugated) cores is well appreciated, less polarizable assemblies of sp3-rich systems with multiple short-range CH···HC contacts between the bulky cyclohexyl and adamantyl moieties are also significantly influenced by electrostatics. Charge penetration is drastically larger in absolute terms for the sp2-rich cores, but still has a non-negligible effect on the sp3-rich dimers, investigated herein, both in terms of their energetics and equilibrium interaction distances. These results emphasize the importance of this electrostatic effect, which has so far been less recognized in aliphatic systems compared to London dispersion, and are therefore likely to have implications for the development of force fields and methods for crystal structure prediction.

Fine-Tuned Organic Photoredox Catalysts for Fragmentation-Alkynylation Cascades of Cyclic Oxime Ethers - Le Vaillant, Franck; Garreau, Marion; Nicolai, Stefano; Gryn'ova, Ganna; Corminboeuf, Clemence; Waser, Jerome (Chemical Science, 2018)
Fine-tuned organic photoredox catalysts are introduced for the metal-free alkynylation of alkylnitrile radicals generated via oxidative ring opening of cyclic alkylketone oxime ethers. The redox properties of the dyes were determined by both cyclic voltammetry and computation and covered an existing gap in the oxidation potential of photoredox organocatalysts.

The Evolution of Multiple Active Site Configurations in a Designed Enzyme - Hong, Nan-Sook; Petrović, Dušan; Lee, Richmond; Gryn'ova, Ganna; Purg, Miha; Saunders, Jake; Bauer, Paul; Carr, Paul D.; Lin, Ching-Yeh; Mabbitt, Peter D.; Zhang, William; Altamore, Timothy; et al. (Nature Communications, 2018)
Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.

Computational Design of pH-Switchable Control Agents for Nitroxide Mediated Polymerization - Gryn'ova, Ganna; Smith, Leesa M.; Coote, Michelle L. (Physical Chemistry Chemical Physics, 2017)
In the present work we use accurate quantum chemistry to evaluate several known and novel nitroxides bearing acid–base groups as pH-switchable control agents for room temperature NMP. Based on G3(MP2,CC)(+)//M06-2X/6-31+G(d) calculations with UAKS-CPCM/M06-2X/6-31+G(d) solvation corrections, a number of novel nitroxides are predicted to be suitable for controlled polymerization of bulk styrene at room temperature when deprotonated (i.e. negatively charged), while remaining inert when neutral. These include an α-ethyl analogue of 3-carboxy-PROXYL and novel derivatives of 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO) that have been modified to include acidic groups. Among the other species evaluated, 3,4-dicarboxy-PROXYL, α-carboxylated PROXYL and the phosphoric acid derivative of N-(2-methylpropyl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-N-oxyl (SG1) are predicted to undergo suitable pH-switching at around 60 °C, and may also be fitting for some applications.

Guidelines and Diagnostics for Charge Carrier Tuning in Thiophene-Based Wires - Gryn'ova, Ganna; Ollitrault, Pauline J.; Corminboeuf, Clémence (Physical Chemistry Chemical Physics, 2017)
Reported experimental trends in charge carrier tuning in single molecule junctions of oligothiophene-based wires are rationalized by means of frontier molecular orbital theory. The length and substituent effects on the energy levels of the frontier orbitals have been shown to translate to the computed transmission spectra – with a caveat of the role of the linker group. The resulting transport (charge carrier) type – n- (electrons) or p- (holes) – is easily identifiable from the in silico charge transfer trends.

Heterotetracenes: Flexible Synthesis and in Silico Assessment of the Hole-Transport Properties - Li, Yifan; Gryn'ova, Ganna; Saenz, Felipe; Jeanbourquin, Xavier; Sivula, Kevin; Corminboeuf, Clémence; Waser, Jérôme (Chemistry - A European Journal, 2017)
Thienoacenes and furoacenes are among the most frequent molecular units found in organic materials. The efficient synthesis of morphologically different heteroacenes and the rapid determination of their solid‐state and electronic properties are still challenging tasks, which slow down progress in the development of new materials. Here, we report a flexible and efficient synthesis of unprecedented heterotetracenes based on a platinum‐ and gold‐catalyzed cyclization–alkynylation domino process using EthynylBenziodoXole (EBX) hypervalent iodine reagents in the key step. The proof‐of‐principle in silico estimation of the synthesized tetracenes’ charge transport properties reveals their strong dependence on both the position and nature of the heteroatoms in the ring system. A broad range of mobility is predicted, with some compounds displaying performance potentially comparable to that of state‐of‐the‐art electronic organic materials.

Enhancing the Power Conversion Efficiency of Dye-Sensitized Solar Cells via Molecular Plasmon-Like Excitations - Li, Jian-Hao; Gryn'ova, Ganna; Prlj, Antonio; Corminboeuf, Clémence (Chemical Communications, 2017)
We introduce a tactic for employing molecular plasmon-like excitations to enhance solar-to-electric power conversion efficiency of dye-sensitized solar cells. We offer general design principles of dimeric dyes, in which a strong plasmonic interaction between two π-conjugated moieties is promoted. The π-stacked conformations of these dimeric dyes result in a desirable broadened absorption and a longer absorption onset wavelength.

Directionality and the Role of Polarization in Electric Field Effects on Radical Stability - Gryn'ova, Ganna; Coote, Michelle L. (Australian Journal of Chemistry, 2017)
ccurate quantum-chemical calculations are used to analyze the effects of charges on the kinetics and thermodynamics of radical reactions, with specific attention given to the origin and directionality of the effects. Conventionally, large effects of the charges are expected to occur in systems with pronounced charge-separated resonance contributors. The nature (stabilization or destabilization) and magnitude of these effects thus depend on the orientation of the interacting multipoles. However, we show that a significant component of the stabilizing effects of the external electric field is largely independent of the orientation of external electric field (e.g. a charged functional group, a point charge, or an electrode) and occurs even in the absence of any pre-existing charge separation. This effect arises from polarization of the electron density of the molecule induced by the electric field. This polarization effect is greater for highly delocalized species such as resonance-stabilized radicals and transition states of radical reactions. We show that this effect on the stability of such species is preserved in chemical reaction energies, leading to lower bond-dissociation energies and barrier heights. Finally, our simplified modelling of the diol dehydratase-catalyzed 1,2-hydroxyl shift indicates that such stabilizing polarization is likely to contribute to the catalytic activity of enzymes.

Charge Transport in Highly Ordered Organic Nanofibrils: Lessons from Modelling - Gryn'ova, Ganna; Nicolaï, Adrien; Prlj, Antonio; Ollitrault, Pauline; Andrienko, Denis; Corminboeuf, Clemence (Journal of Materials Chemistry C, 2017)
H-Aggregates featuring tight π-stacks of the conjugated heterocyclic cores represent ideal morphologies for 1D organic semiconductors. Such nanofibrils have larger electronic couplings between the adjacent cores compared to the herringbone crystal or amorphous assemblies. In this work, we show that for a set of seven structurally and electronically distinct cores, including quaterthiophene and oligothienoacenes, the co-planar dimer model captures the impact of the monomer's electronic structure on charge transport, but more advanced multiscale modelling, featuring molecular dynamics and kinetic Monte-Carlo simulations, is needed to account for the packing and disorder effects. The differences in the results between these two computational approaches arise from the sensitivity of the electronic coupling strength to the relative alignment of adjacent cores, in particular the long-axis shift between them, imposed by the oligopeptide side chains. Our results demonstrate the dependence of the performance of H-aggregates on the chemical nature of the cores and the presence of the side chains, as well as the limitations in using the simple dimer model for a rapid computational pre-screening of the conjugated cores.

Implications of Charge Penetration for Heteroatom-Containing Organic Semiconductors - Gryn'ova, Ganna; Corminboeuf, Clemence (The Journal of Physical Chemistry Letters, 2016)
The noncovalent interactions of neutral π-conjugated cores, pertinent to organic semiconductor materials, are intimately related to their charge transport properties and involve a subtle interplay of dispersion, Pauli repulsion, and electrostatic contributions. Realizing structural arrangements that are both energetically preferred and sufficiently conductive is a challenge. We tackle this problem by means of charge penetration contribution to the interaction energy, boosted in systems containing large heteroatoms (e.g., sulfur, selenium, phosphorus, silicon, and arsenic). We find that in both the model and “realistic” dimers of such heteroatom-containing cores dispersion is balanced out by the exchange and interaction energy is instead governed by substantial charge penetration. These systems also feature stronger electronic couplings compared to the dispersion-driven dimers of oligoacenes and/or the herringbone assemblies. Thus, charge penetration, enhanced in the π-conjugated cores comprising larger heteroatoms, arises as an attractive strategy toward potentially more stable and efficient organic electronic materials.

Why Are sec-Alkylperoxyl Bimolecular Self-Reactions Orders of Magnitude Faster than the Analogous Reactions of tert-Alkylperoxyls? The Unanticipated Role of CH Hydrogen Bond Donation - Lee, Richmond; Gryn'ova, Ganna; Ingold, K. U.; Coote, Michelle L. (Physical Chemistry Chemical Physics, 2016)
High-level ab initio calculations are used to identify the mechanism of secondary (and primary) alkylperoxyl radical termination and explain why their reactions are much faster than their tertiary counterparts. Contrary to existing literature, the decomposition of both tertiary and non-tertiary tetroxides follows the same asymmetric two-step bond cleavage pathway to form a caged intermediate of overall singlet multiplicity comprising triplet oxygen and two alkoxyl radicals. The alpha hydrogen atoms of non-tertiary species facilitate this process by forming unexpected CH⋯O hydrogen bonds to the evolving O2. For non-tertiary peroxyls, subsequent alpha hydrogen atom transfer then yields the experimentally observed non-radical products, ketone, alcohol and O2, whereas for tertiary species, this reaction is precluded and cage escape of the (unpaired) alkoxyl radicals is a likely outcome with important consequences for autoxidation.

Entropy-Driven Selectivity for Chain Scission: Where Macromolecules Cleave - Pahnke, Kai; Brandt, Josef; Gryn'ova, Ganna; Lin, Ching Y.; Altintas, Ozcan; Schmidt, Patrick; Lederer, Albena; Coote, Michelle L.; Barner-Kowollik, Christopher (Angewandte Chemie International Edition, 2016)
We show that, all other conditions being equal, bond cleavage in the middle of molecules is entropically much more favored than bond cleavage at the end. Multiple experimental and theoretical approaches have been used to study the selectivity for bond cleavage or dissociation in the middle versus the end of both covalent and supramolecular adducts and the extensive implications for other fields of chemistry including, e.g., chain transfer, polymer degradation, and control agent addition are discussed. The observed effects, which are a consequence of the underlying entropic factors, were predicted on the basis of simple theoretical models and demonstrated via high‐temperature (HT) NMR spectroscopy of self‐assembled supramolecular diblock systems as well as temperature‐dependent size‐exclusion chromatography (TD SEC) of covalently bonded Diels–Alder step‐growth polymers.

Theory and Practice of Uncommon Molecular Electronic Configurations - Gryn'ova, Ganna; Coote, Michelle L.; Corminboeuf, Clemence (Wiley Interdisciplinary Reviews: Computational Molecular Science, 2015)
The electronic configuration of the molecule is the foundation of its structure and reactivity. The spin state is one of the key characteristics arising from the ordering of electrons within the molecule's set of orbitals. Organic molecules that have open‐shell ground states and interesting physicochemical properties, particularly those influencing their spin alignment, are of immense interest within the up‐and‐coming field of molecular electronics. In this advanced review, we scrutinize various qualitative rules of orbital occupation and spin alignment, viz., the aufbau principle, Hund's multiplicity rule, and dynamic spin polarization concept, through the prism of quantum mechanics. While such rules hold in selected simple cases, in general the spin state of a system depends on a combination of electronic factors that include Coulomb and Pauli repulsion, nuclear attraction, kinetic energy, orbital relaxation, and static correlation. A number of fascinating chemical systems with spin states that fluctuate between triplet and open‐shell singlet, and are responsive to irradiation, pH, and other external stimuli, are highlighted. In addition, we outline a range of organic molecules with intriguing non‐aufbau orbital configurations. In such quasi‐closed‐shell systems, the singly occupied molecular orbital (SOMO) is energetically lower than one or more doubly occupied orbitals. As a result, the SOMO is not affected by electron attachment to or removal from the molecule, and the products of such redox processes are polyradicals. These peculiar species possess attractive conductive and magnetic properties, and a number of them that have already been developed into molecular electronics applications are highlighted in this review.

Experimental Demonstration of pH-Dependent Electrostatic Catalysis of Radical Reactions - Klinska, Marta; Smith, Leesa M.; Gryn'ova, Ganna; Banwell, Martin G.; Coote, Michelle L. (Chemical Science, 2015)
Time-dependent fluorescence spectroscopy has been used to demonstrate significant pH-dependent electrostatic effects on the kinetics and thermodynamics of hydrogen atom transfer between 1-hydroxy-2,2,6,6-tetramethyl-4-piperidinecarboxylic acid (4-CT-H) and the profluorescent nitroxide {2,2,6,6-tetramethyl-4-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-1-piperidinyl}oxidanyl radical (PFN) in dichloromethane. This pH switching does not occur when 4-CT-H is replaced with a structurally analogous hydroxylamine that lacks an acid-base group, or when the polarity of the solvent is increased. These findings validate our recent theoretical predictions that electrostatic stabilisation of delocalised radicals is of functional significance in low polarity environments.

Entropy-Driven Chain Effects on Ligation Chemistry - Pahnke, Kai; Brandt, Josef; Gryn'ova, Ganna; Lindner, Peter; Schweins, Ralf; Schmidt, Patrick; Lederer, Albena; Coote, Michelle L.; Barner-Kowollik, Christopher (Chemical Science, 2015)
We report the investigation of fundamental entropic chain effects that enable the tuning of modular ligation chemistry – for example dynamic Diels–Alder (DA) reactions in materials applications – not only classically via the chemistry of the applied reaction sites, but also via the physical and steric properties of the molecules that are being joined. Having a substantial impact on the reaction equilibrium of the reversible ligation chemistry, these effects are important when transferring reactions from small molecule studies to larger or other entropically very dissimilar systems. The effects on the DA equilibrium and thus the temperature dependent degree of debonding (%debond) of different cyclopentadienyl (di-)functional poly(meth-)acrylate backbones (poly(methyl methacrylate), poly(iso-butyl methacrylate), poly(tert-butyl methacrylate), poly(iso-butyl acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(methyl acrylate) and poly(isobornyl acrylate)), linked via a difunctional cyanodithioester (CDTE) were examined via high temperature (HT) NMR spectroscopy as well as temperature dependent (TD) SEC measurements. A significant impact of not only chain mass and length with a difference in the degree of debonding of up to 30% for different lengths of macromonomers of the same polymer type but – remarkably – as well the chain stiffness with a difference in bonding degrees of nearly 20% for isomeric poly(butyl acrylates) is found. The results were predicted, reproduced and interpreted via quantum chemical calculations, leading to a better understanding of the underlying entropic principles.

Chemical Shift and Coupling Constant Analysis of Dibenzyloxy Disulfides - Stoutenburg, Eric G.; Gryn'ova, Ganna; Coote, Michelle L.; Priefer, Ronny (Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015)
Dialkoxy disulfides have found applications in the realm of organic synthesis as an S2 or alkoxy donor, under thermal and photolytic decompositions conditions, respectively. Spectrally, dibenzyloxy disulfides possess an ABq in the 1H NMR, which can shift by over 1.1 ppm depending on the substituents present on the aromatic ring, as well as the solvent employed. The effect of the said substituents and solvent were analyzed and compared to the center of the ABq, geminal coupling, and the differences in chemical shifts of the individual doublets. Additionally, quantum-chemical calculations demonstrated the intramolecular H-bonding arrangement, found within the dibenzyloxy disulfides.

Experimental Evidence for Competitive N-O and O-C Bond Homolysis in Gas-Phase Alkoxyamines - Marshall, David L.; Gryn'ova, Ganna; Coote, Michelle L.; Barker, Philip J.; Blanksby, Stephen J. (International Journal of Mass Spectrometry, 2015)
The extensive use of alkoxyamines in controlled radical polymerisation and polymer stabilisation is based on rapid cycling between the alkoxyamine (R1R2NOR3) and a stable nitroxyl radical (R1R2NO•) via homolysis of the labile OC bond. Competing homolysis of the alkoxyamine NO bond has been predicted to occur for some substituents leading to production of aminyl and alkoxyl radicals. This intrinsic competition between the OC and NO bond homolysis processes has to this point been difficult to probe experimentally. Herein we examine the effect of local molecular structure on the competition between NO and OC bond cleavage in the gas phase by variable energy tandem mass spectrometry in a triple quadrupole mass spectrometer. A suite of cyclic alkoxyamines with remote carboxylic acid moieties (HOOCR1R2NOR3) were synthesised and subjected to negative ion electrospray ionisation to yield [M − H]− anions where the charge is remote from the alkoxyamine moiety. Collision-induced dissociation of these anions yield product ions resulting, almost exclusively, from homolysis of OC and/or NO bonds. The relative efficacy of NO and OC bond homolysis was examined for alkoxyamines incorporating different R3 substituents by varying the potential difference applied to the collision cell, and comparing dissociation thresholds of each product ion channel. For most R3 substituents, product ions from homolysis of the OC bond are observed and product ions resulting from cleavage of the NO bond are minor or absent. A limited number of examples were encountered however, where NO homolysis is a competitive dissociation pathway because the OC bond is stabilised by adjacent heteroatom(s) (e.g. R3 = CH2F). The dissociation threshold energies were compared for different alkoxyamine substituents (R3) and the relative ordering of these experimentally determined energies is shown to correlate with the bond dissociation free energies, calculated by ab initio methods. Understanding the structure-dependent relationship between these rival processes will assist in the design and selection of alkoxyamine motifs that selectively promote the desirable OC homolysis pathway.

Mechanisms and Energetics of Potassium Channel Block by Local Anesthetics and Antifungal Agents - Chen, Rong; Gryn'ova, Ganna; Wu, Yingliang; Coote, Michelle L.; Chung, Shin-Ho (Biochemistry, 2014)
Many drug molecules inhibit the conduction of several families of cation channels by binding to a small cavity just below the selectivity filter of the channel protein. The exact mechanisms governing drug–channel binding and the subsequent inhibition of conduction are not well understood. Here the inhibition of two K+ channel isoforms, Kv1.2 and KCa3.1, by two drug molecules, lidocaine and TRAM-34, is examined in atomic detail using molecular dynamics simulations. A conserved valine-alanine-valine motif in the inner cavity is found to be crucial for drug binding in both channels, consistent with previous studies of similar systems. Potential of mean force calculations show that lidocaine in its charged form creates an energy barrier of ∼6 kT for a permeating K+ ion when the ion is crossing over the drug, while the neutral form of lidocaine has no significant effect on the energetics of ion permeation. On the other hand, TRAM-34 in the neutral form is able to create a large energy barrier of ∼10 kT by causing the permeating ion to dehydrate. Our results suggest that TRAM-34 analogues that remain neutral and permeable to membranes under acidic conditions common to inflammation may act as possible drug scaffolds for combating local anesthetic failure in inflammation.

Desorption Electrospray Ionisation Mass Spectrometry of Stabilised Polyesters Reveals Activation of Hindered Amine Light Stabilisers - Paine, Martin R.L.; Gryn'ova, Ganna; Coote, Michelle L.; Barker, Philip J.; Blanksby, Stephen J. (Polymer Degradation and Stability, 2014)
The use of hindered amine light stabilizers (HALS) to retard thermo- and photo-degradation of polymers has become increasingly common. Proposed mechanisms of polymer stabilisation involve significant changes to the HALS chemical structure; however, reports of the characterisation of these modified chemical species are limited. To better understand the fate of HALS and determine their in situ modifications, desorption electrospray ionisation mass spectrometry (DESI-MS) was employed to characterise ten commercially available HALS present in polyester-based coil coatings. TINUVIN® 770, 292, 144, 123, 152, and NOR371; HOSTAVIN® 3052, 3055, 3050, and 3058 were separately formulated with a pigmented, thermosetting polyester resin, cured on metal at 262 °C and analysed directly by DESI-MS. High-level ab initio molecular orbital theory calculations were also undertaken to aid the mechanistic interpretation of the results. For HALS containing N-substituted piperidines (i.e., N–CH3, N–C(O)CH3, and N–OR) a secondary piperidine (N–H) analogue was detected in all cases. The formation of these intermediates can be explained either through hydrogen abstraction based mechanisms or direct N–OR homolysis with the former dominant under normal service temperatures (ca. 25–80 °C), and the latter potentially becoming competitive under the high temperatures associated with curing (ca. 230–260 °C).

Origin and Scope of Long-Range Stabilizing Interactions and Associated SOMO–HOMO Conversion in Distonic Radical Anions - Gryn'ova, Ganna; Coote, Michelle L. (Journal of the American Chemical Society, 2013)
High-level quantum-chemical methods have been used to study the scope and physical origin of the significant long-range stabilizing interactions between nonmutually conjugated anion and radical moieties in SOMO–HOMO converted distonic radical anions. In such species, deprotonation of the acid fragment can stabilize the remote radical by tens of kilojoules, or, analogously, formation of a stable radical (by abstraction or homolytic cleavage reactions) increases the acidity of a remote acid by several pKa units. This stabilization can be broadly classified as a new type of polar effect that originates in Coloumbic interactions but, in contrast to standard polar effects, persists in radicals with no charge-separated (i.e., dipole) resonance contributors, is nondirectional, and hence of extremely broad scope. The stabilization upon deprotonation is largest when a highly delocalized radical is combined with an initially less stable anion (i.e., the conjugate base of a weaker acid), and is negligible for highly localized radicals and/or stable anions. The effect is largest in the gas phase and low-polarity solvents but is quenched in water, where the anion is sufficiently stabilized. These simple rules can be employed to design various switchable compounds able to reversibly release radicals in response to pH for use in, for example, organic synthesis or nitroxide-mediated polymerization. Moreover, given its wide chemical scope, this effect is likely to influence the protonation state of many biological substrates under radical attack and may contribute to enzyme catalysis.

Which Side-Reactions Compromise Nitroxide Mediated Polymerization? - Gryn'ova, Ganna; Lin, Ching Yeh; Coote, Michelle L. (Polymer Chemistry, 2013)
The mechanism of the nitroxide mediated polymerization (NMP) is well understood, however less is known about the side-reactions that interfere and in certain cases severely compromise it. Experimental studies inevitably involve model fitting leading to at times contradictory conclusions as to which elementary side-reactions are behind the failure of a given NMP system. In the present work we use high-level quantum-chemical calculations to obtain the rate coefficients of the various side-reactions, both suggested previously and considered here for the first time, and first principles PREDICI kinetic simulations to identify the most deleterious side-reactions involved in the TEMPO, SG1 and DPAIO mediated polymerization of styrene, acrylate and methacrylate monomers. We show that the core mechanism for the thermal decomposition of alkoxyamines differs between the uni- and polymeric species, which often makes such experiments not suitable for modelling the NMP conditions. We also find that the main side-reaction responsible for the failure of TEMPO and SG1 in methacrylate homopolymerization is an intramolecular alkoxyamine decomposition (often referred to as ‘disproportionation’) via a Cope-type elimination, however in the case of SG1 the polymerization outcome is additionally affected by the equilibrium constant of alkoxyamine bond homolysis. On the basis of these findings, complemented by a thorough analysis of available experimental data, we define guidelines for minimising occurrence of the side-reactions and thus improving NMP. Finally, the accurate first principles rate parameters reported in this study should prove useful for subsequent kinetic modelling oriented at optimising different polymerization conditions.

Switching Radical Stability by pH-Induced Orbital Conversion - Gryn'ova, Ganna; Marshall, David L.; Blanksby, Stephen J.; Coote, Michelle L. (Nature Chemistry, 2013)
In most radicals the singly occupied molecular orbital (SOMO) is the highest-energy occupied molecular orbital (HOMO); however, in a small number of reported compounds this is not the case. In the present work we expand significantly the scope of this phenomenon, known as SOMO–HOMO energy-level conversion, by showing that it occurs in virtually any distonic radical anion that contains a sufficiently stabilized radical (aminoxyl, peroxyl, aminyl) non-π-conjugated with a negative charge (carboxylate, phosphate, sulfate). Moreover, regular orbital order is restored on protonation of the anionic fragment, and hence the orbital configuration can be switched by pH. Most importantly, our theoretical and experimental results reveal a dramatically higher radical stability and proton acidity of such distonic radical anions. Changing radical stability by 3–4 orders of magnitude using pH-induced orbital conversion opens a variety of attractive industrial applications, including pH-switchable nitroxide-mediated polymerization, and it might be exploited in nature.

Computational Evaluation of the Sulfonyl Radical as a Universal Leaving Group for RAFT Polymerisation - Gryn'ova, Ganna; Guliashvili, Tamaz; Matyjaszewski, Krzysztof; Coote, Michelle L. (Australian Journal of Chemistry, 2013)
The present study investigates the performance of the sulfonyl radical, i.e. •SO2Ph, as a universal leaving group in reversible addition–fragmentation chain-transfer (RAFT) polymerisation. The sulfonyl radical is widely used as a radical initiator and has already been proved successful as a leaving group in an atom-transfer radical polymerisation. Our results, obtained using high-level ab initio computational methodology under relevant experimental conditions, indicate superior performance of the sulfonyl compared with a reference cyanoisopropyl group in controlling RAFT of a wide range of monomers. Importantly, the presence of sulfonyl chain ends in the polymers so formed opens attractive possibilities for further functionalisation. Potential synthetic routes to the R-sulfonyl RAFT agents are discussed.

New Insights into the Mechanism of Amine/Nitroxide Cycling during the Hindered Amine Light Stabilizer Inhibited Oxidative Degradation of Polymers - Gryn'ova, Ganna; Ingold, K. U.; Coote, Michelle L. (Journal of the American Chemical Society, 2012)
High-level ab initio molecular orbital theory calculations are used to identify the origin of the remarkably high inhibition stoichiometric factors exhibited by dialkylamine-based radical-trapping antioxidants. We have calculated the free energy barriers and reaction energies at 25, 80, and 260 °C in the gas phase and in aqueous solution for a broad range of reactions that might, potentially, be involved in amine/nitroxide cycling, as well as several novel pathways proposed as part of the present work, including that of N-alkyl hindered amine light stabilizer activation. We find that most of the literature nitroxide regeneration cycles should be discarded on either kinetic or thermodynamic grounds; some are even inconsistent with existing experimental observations. We therefore propose a new mechanistic cycle that relies on abstraction of a β-hydrogen atom from an alkoxyamine (R1R2NOCHR3R4). Our results suggest that this cycle is energetically feasible for a range of substrates and provides an explanation for previously misinterpreted or unexplained experimental results. We also explore alternative mechanisms for amine/nitroxide cycling for cases where the alkoxyamines do not possess an abstractable β-hydrogen.

Computational Design of Cyclic Nitroxides as Efficient Redox Mediators for Dye-Sensitized Solar Cells - Gryn'ova, Ganna; Barakat, Jonathan M.; Blinco, James P.; Bottle, Steven E.; Coote, Michelle L. (Chemistry - A European Journal, 2012)
Cyclic nitroxide radicals represent promising alternatives to the iodine‐based redox mediator commonly used in dye‐sensitized solar cells (DSSCs). To date DSSCs with nitroxide‐based redox mediators have achieved energy conversion efficiencies of just over 5 % but efficiencies of over 15 % might be achievable, given an appropriate mediator. The efficacy of the mediator depends upon two main factors: it must reversibly undergo one‐electron oxidation and it must possess an oxidation potential in a range of 0.600–0.850 V (vs. a standard hydrogen electrode (SHE) in acetonitrile at 25 °C). Herein, we have examined the effect that structural modifications have on the value of the oxidation potential of cyclic nitroxides as well as the reversibility of the oxidation process. These included alterations to the N‐containing skeleton (pyrrolidine, piperidine, isoindoline, azaphenalene, etc.), as well as the introduction of different substituents (alkyl‐, methoxy‐, amino‐, carboxy‐, etc.) to the ring. Standard oxidation potentials were calculated using high‐level ab initio methodology that was demonstrated to be very accurate (with a mean absolute deviation from experimental values of only 16 mV). An optimal value of 1.45 for the electrostatic scaling factor for UAKS radii in acetonitrile solution was obtained. Established trends in the values of oxidation potentials were used to guide molecular design of stable nitroxides with desired equation image, and a number of compounds were suggested for potential use as enhanced redox mediators in DSSCs.

Reversible Addition–Fragmentation Chain Transfer Polymerization of Vinyl Chloride - Abreu, Carlos M. R.; Mendonça, Patrícia V.; Serra, Arménio C.; Coelho, Jorge F. J.; Popov, Anatoliy V.; Gryn'ova, Ganna; Coote, Michelle L.; Guliashvili, Tamaz (Macromolecules, 2012)
Controlled/“living” radical polymerization (CLRP) of vinyl chloride (VC) via the reversible addition–fragmentation chain transfer (RAFT) process is reported for the first time. The cyanomethyl methyl(phenyl)carbamodithioate (CMPCD) was found to be an efficient RAFT agent enabling the CLRP polymerization of VC monomer under certain experimental conditions. Two different radical initiators, having very distinct half-life times at room temperature, were employed in this study. The kinetic studies of RAFT polymerization of VC show a linear increase of the molecular weight with the monomer conversion and the lowest polydispersity (PDI) ever reported for poly(vinyl chloride) (PVC) synthesized with CLRP method (PDI ∼ 1.4). The resulting PVC was fully characterized using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), 1H nuclear magnetic resonance spectroscopy (1H NMR), and gel permeation chromatography (GPC) techniques. The 1H NMR and MALDI-TOF-MS analysis of PVC prepared via RAFT polymerization method have shown the absence of structural defects and the presence of chain-end functional groups. The “livingness” of the PVC was also confirmed by a successful reinitiation experiment. The suitability of the RAFT agent was also confirmed via high-level ab initio molecular orbital calculations.

Revising the Mechanism of Polymer Autooxidation - Gryn'ova, Ganna; Hodgson, Jennifer L.; Coote, Michelle L. (Org. Biomol. Chem., 2011)
The basic scheme for autooxidation of polymers, originally developed by Bolland, Gee and co-workers for rubbers and lipids, is now widely applied to all types of polymeric materials. According to their scheme, the reaction that makes this process autocatalytic, referred to as the propagation step, is a hydrogen abstraction from the next substrate by the peroxyl radical (ROO˙ + RH → ROOH + R˙). In this study, using advanced quantum-chemical methods, we have shown that this step is actually characterised by largely positive Gibbs free energy (10–65 kJ mol−1) for most regular polymers with saturated chains (polypropylene, polyethylene, polyvinyl chloride, polyvinyl acetate, polyurethane, poly(methyl methacrylate)etc.) and even some polymers with unsaturated fragments (polystyrene, polyethylene terephthalate). Neither elevated temperature, nor solvation makes this process thermodynamically favourable. Only when the formed radical centre is conjugated with adjacent double bonds (as in polybutadiene) or captodatively stabilised by two suitable functional groups (such as a carbonyl and a lone pair donor such as oxygen or nitrogen), is the propagation step exoergic. Instead, we show that it is the presence of structural defects, such as terminal or internal double bonds, formed either during polymerisation or in the degradation process itself, that is responsible for the autooxidation of most polyesters and most polyalkenes. Recognition of the real mechanism of autooxidation in polymers is a key to developing strategies for the prevention of their degradation.

The Use of Spin Traps for the Kinetic Investigation of Elementary Events of Pseudoliving Radical Reversible Addition-Fragmentation Chain-Transfer Polymerization - Golubev, V. B.; Filippov, A. N.; Chernikova, E. V.; Coote, M. L.; Lin, C. Y.; Gryn'ova, Ganna (Polymer Science Series C, 2011)
The spin-trapping technique is used for the first time to study the kinetics and mechanism of addition and fragmentation elementary events in reversible addition-fragmentation chain-transfer pseudoliving radical polymerization. As shown by the example of the spin-trap-reversible addition-fragmentation chaintransfer agent model system, the constants of addition (substitution) of the model tert-butyl radical to polymeric reversible addition-fragmentation chain-transfer agents (poly(styrene dithiobenzoate), poly(n-butyl acrylate) dithiobenzoate, etc.) are one to two orders of magnitude higher than the constants of addition reactions involving low-molecular-mass reversible addition-fragmentation chain-transfer agents (tert-butyl dithiobenzoate, benzyl dithiobenzoate, di-tert-butyl trithiocarbonate, and dibenzyl trithiocarbonate). This circumstance makes it possible to significantly widen the synthetic possibilities of reversible addition-fragmentation chain-transfer polymerization. Rate constants of the fragmentation reaction for a number of intermediates are estimated, and the relationship between their structure and stability is ascertained. For the model reaction of the interaction (addition and fragmentation) of the tert-butyl radical with low-molecular-mass reversible addition-fragmentation chain-transfer agents, equilibrium constants are calculated via the methods of computational chemistry.

Oxidation of 4-Substituted TEMPO Derivatives Reveals Modifications at the 1- and 4-Positions - Marshall, David L.; Christian, Meganne L.; Gryn'ova, Ganna; Coote, Michelle L.; Barker, Philip J.; Blanksby, Stephen J. (Organic & Biomolecular Chemistry, 2011)
Potenital pathways for the deactivation of hindered amine light stabilisers (HALS) have been investigated by observing reactions of model compounds—based on 4-substituted derivatives of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)—with hydroxyl radicals. In these reactions, dilute aqueous suspensions of photocatalytic nanoparticulate titanium dioxide were irradiated with UV light in the presence of water-soluble TEMPO derivatives. Electron spin resonance (ESR) and electrospray ionisation mass-spectrometry (ESI-MS) data were acquired to provide complementary structural elucidation of the odd- and even-electron products of these reactions and both techniques show evidence for the formation of 4-oxo-TEMPO (TEMPONE). TEMPONE formation from the 4-substituted TEMPO compounds is proposed to be initiated by hydrogen abstraction at the 4-position by hydroxyl radical. High-level ab initio calculations reveal a thermodynamic preference for abstraction of this hydrogen but computed activation barriers indicate that, although viable, it is less favoured than hydrogen abstraction from elsewhere on the TEMPO scaffold. If a radical is formed at the 4-position however, calculations elucidate two reaction pathways leading to TEMPONE following combination with either a second hydroxyl radical or dioxygen. An alternate mechanism for conversion of TEMPOL to TEMPONEvia an alkoxyl radical intermediate is also considered and found to be competitive with the other pathways. ESI-MS analysis also shows an increased abundance of analogous 4-substituted piperidines during the course of irradiation, suggesting competitive modification at the 1-position to produce a secondary amine. This modification is confirmed by characteristic fragmentation patterns of the ionised piperidines obtained by tandem mass spectrometry. The conclusions describe how reaction at the 4-position could be responsible for the gradual depletion of HALS in pigmented surface coatings and secondly, that modification at nitrogen to form the corresponding secondary amine species may play a greater role in the stabilisation mechanisms of HALS than previously considered.

Evaluation of the Dependence of Aqueous Solubility of Nitro Compounds on Temperature and Salinity: A COSMO-RS Simulation - Kholod, Yana A.; Gryn'ova, Ganna; Gorb, Leonid; Hill, Frances C.; Leszczynski, Jerzy (Chemosphere, 2011)
The solubility in pure and saline water at various temperatures was calculated for selected nitro compounds (nitrobenzene, 1,3,5-trinitrobenzene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2,3-dinitrotoluene, 3,4-dinitrotoluene, 2,4,6-trinitrotoluene) using the Conductor-like Screening model for Real Solvents (COSMO-RS). The results obtained were compared with experimental values. The COSMO-RS predictions have shown high accuracy in reproducing the trends of aqueous solubilities for both temperature and salinity. The proposed methodology was then applied to predict the aqueous solubilities of 19 nitro compounds in the temperature range of 5–50 °C in saline solutions. The salting-out parameters of the Setschenow equation were also calculated. The predicted salting-out parameters were overestimated when compared to the measured values, but these parameters can still be used for qualitative estimation of the trends.

Unusual Complexes of Trapped Methanol with Azacryptands - Hossain, Md. Alamgir; Saeed, Musabbir A.; Gryn'ova, Ganna; Powell, Douglas R.; Leszczynski, Jerzy (CrystEngComm, 2010)
Structural analysis of sulfate complexes of two different azacryptands crystallized under identical conditions in the presence of methanol and water reveals that one methanol is selectively trapped in each cavity, assisted by the specific arrangements of three external sulfates close to one tren unit.

Use of Spin Trap Technique for Kinetic Investigation of Elementary Steps of RAFT-Polymerization - Filippov, Anatoly; Chernikova, Elena; Golubev, Vladimir; Gryn'ova, Ganna; Yeh, Ching; L., Michelle (Nitroxides - Theory, Experiment and Applications, 2012)

KBbox: A Toolbox of Computational Methods for Studying the Kinetics of Molecular Binding - Bruce, Neil J.; Ganotra, Gaurav K.; Richter, Stefan; Wade, Rebecca C. (Journal of Chemical Information and Modeling, 2019)

Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals - Bruce, Neil J.; Narzi, Daniele; Trpevski, Daniel; van Keulen, Siri C.; Nair, Anu G.; Röthlisberger, Ursula; Wade, Rebecca C.; Carloni, Paolo; Hellgren Kotaleski, Jeanette (PLOS Computational Biology, 2019)

Machine Learning Analysis of τRAMD Trajectories to Decipher Molecular Determinants of Drug-Target Residence Times - Kokh, Daria; Kaufmann, Tom; Kister, Bastian; Wade, Rebecca C. (Frontiers in Molecular Biosciences, 2019)

Allostery in Its Many Disguises: From Theory to Applications - Wodak, Shoshana J.; Paci, Emanuele; Dokholyan, Nikolay V.; Berezovsky, Igor N.; Horovitz, Amnon; Li, Jing; Hilser, Vincent J.; Bahar, Ivet; Karanicolas, John; Stock, Gerhard; Hamm, Peter; Stote, Roland H.; et al. (Structure, 2019)

Influence of Transmembrane Helix Mutations on Cytochrome P450-Membrane Interactions and Function - Mustafa, Ghulam; Nandekar, Prajwal P.; Camp, Tyler J.; Bruce, Neil J.; Gregory, Michael C.; Sligar, Stephen G.; Wade, Rebecca C. (Biophysical Journal, 2019)

Molecular Modeling in Drug Design - Wade, Rebecca C.; Salo-Ahen, Outi (Molecules, 2019)

What determines docking performance in drug discovery? A case study of PTR1, an anti-parasitic target - Pöhner, Ina; Panecka, Joanna; Wade, Rebecca C. (Journal of Cheminformatics, 2016)

Docking of DNA duplexes on a gold surface - Rosa, Marta; Kokh, Daria; Corni, Stefano; Wade, Rebecca C.; Felice, Rosa Di (Journal of Self-Assembly and Molecular Electronics (SAME), 2015)

On the application of the MARTINI coarse-grained model to immersion of a protein in a phospholipid bilayer - Mustafa, Ghulam; Nandekar, Prajwal P.; Yu, Xiaofeng; Wade, Rebecca C. (The Journal of Chemical Physics, 2015)

Conservation and Role of Electrostatics in Thymidylate Synthase - Garg, Divita; Skouloubris, Stephane; Briffotaux, Julien; Myllykallio, Hannu; Wade, Rebecca C. (Scientific Reports, 2015)

When the Label Matters: Adsorption of Labeled and Unlabeled Proteins on Charged Surfaces - Romanowska, Julia; Kokh, Daria; Wade, Rebecca C. (Nano Letters, 2015)

Molecular simulations reveal that the long range fluctuations of human DPP III change upon ligand binding - Tomić, A.; Berynskyy, M.; Wade, Rebecca C.; Tomić, S. (Molecular BioSystems, 2015)

Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation - Nillegoda, Nadinath B.; Kirstein, Janine; Szlachcic, Anna; Berynskyy, Mykhaylo; Stank, Antonia; Stengel, Florian; Arnsburg, Kristin; Gao, Xuechao; Scior, Annika; Aebersold, Ruedi; Guilbride, D. Lys; Wade, Rebecca C.; et al. (Nature, 2015)

A multiscale approach to simulating the conformational properties of unbound multi-C2H2 zinc finger proteins - Liu, Lei; Wade, Rebecca C.; Heermann, Dieter W. (Proteins: Structure, Function, and Bioinformatics, 2015)

SDA 7: A modular and parallel implementation of the simulation of diffusional association software - Martinez, Michael; Bruce, Neil J.; Romanowska, Julia; Kokh, Daria; Ozboyaci, Musa; Yu, Xiaofeng; Öztürk, Mehmet Ali; Richter, Stefan; Wade, Rebecca C. (Journal of Computational Chemistry, 2015)

Molecular identification and functional characterization of the first Nα-acetyltransferase in plastids by global acetylome profiling - Dinh, Trinh V.; Bienvenut, Willy V.; Linster, Eric; Feldman-Salit, Anna; Jung, Vincent A.; Meinnel, Thierry; Hell, Rüdiger; Giglione, Carmela; Wirtz, Markus (PROTEOMICS, 2015)

Kar1 binding to Sfi1 C-terminal regions anchors the SPB bridge to the nuclear envelope - Seybold, Christian; Elserafy, Menattallah; Rüthnick, Diana; Ozboyaci, Musa; Neuner, Annett; Flottmann, Benjamin; Heilemann, Mike; Wade, Rebecca C.; Schiebel, Elmar (The Journal of Cell Biology, 2015)

webSDA: a web server to simulate macromolecular diffusional association - Yu, Xiaofeng; Martinez, Michael; Gable, Annika L.; Fuller, Jonathan C.; Bruce, Neil J.; Richter, Stefan; Wade, Rebecca C. (Nucleic Acids Research, 2015)

Hotspots in an Obligate Homodimeric Anticancer Target. Structural and Functional Effects of Interfacial Mutations in Human Thymidylate Synthase - Salo-Ahen, Outi M. H.; Tochowicz, Anna; Pozzi, Cecilia; Cardinale, Daniela; Ferrari, Stefania; Boum, Yap; Mangani, Stefano; Stroud, Robert M.; Saxena, Puneet; Myllykallio, Hannu; Costi, Maria Paola; Ponterini, Glauco; et al. (Journal of Medicinal Chemistry, 2015)

Modelling of solvation effects for brownian dynamics simulation of biomolecular recognition. - Bruce, Neil J.; Kokh, Daria; Ozboyaci, Musa; Wade, Rebecca C. (2015)

Computational Approaches for Studying Drug Binding Kinetics - Romanowska, Julia; Kokh, Daria; Fuller, Jonathan C.; Wade, Rebecca C. (Thermodynamics and Kinetics of Drug Binding, 2015)

Dynamics of CYP51: implications for function and inhibitor design - Yu, Xiaofeng; Cojocaru, Vlad; Mustafa, Ghulam; Salo-Ahen, Outi M. H.; Lepesheva, Galina I.; Wade, Rebecca C. (Journal of Molecular Recognition, 2015)

LigDig: a web server for querying ligand–protein interactions - Fuller, Jonathan C.; Martinez, Michael; Henrich, Stefan; Stank, Antonia; Richter, Stefan; Wade, Rebecca C. (Bioinformatics, 2015)

Long range Debye-Hückel correction for computation of grid-based electrostatic forces between biomacromolecules - Mereghetti, Paolo; Martinez, Michael; Wade, Rebecca C. (BMC Biophysics, 2014)

On Calculation of the Electrostatic Potential of a Phosphatidylinositol Phosphate-Containing Phosphatidylcholine Lipid Membrane Accounting for Membrane Dynamics - Fuller, Jonathan C.; Martinez, Michael; Wade, Rebecca C. (PLoS ONE, 2014)

Drug Metabolism Prediction - Mustafa, Ghulam; Yu, Xiaofeng; Wade, Rebecca C. (2014)

GTP regulates the microtubule nucleation activity of γ-tubulin - Gombos, Linda; Neuner, Annett; Berynskyy, Mykhaylo; Fava, Luca L.; Wade, Rebecca C.; Sachse, Carsten; Schiebel, Elmar (Nature Cell Biology, 2013)

Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding - Sandikci, Arzu; Gloge, Felix; Martinez, Michael; Mayer, Matthias P; Wade, Rebecca C.; Bukau, Bernd; Kramer, Günter (Nature Structural & Molecular Biology, 2013)

Organism-Adapted Specificity of the Allosteric Regulation of Pyruvate Kinase in Lactic Acid Bacteria - Veith, Nadine; Feldman-Salit, Anna; Cojocaru, Vlad; Henrich, Stefan; Kummer, Ursula; Wade, Rebecca C. (PLoS Computational Biology, 2013)

Regulation of the Activity of Lactate Dehydrogenases from Four Lactic Acid Bacteria - Feldman-Salit, Anna; Hering, Silvio; Messiha, Hanan L.; Veith, Nadine; Cojocaru, Vlad; Sieg, Antje; Westerhoff, Hans V.; Kreikemeyer, Bernd; Wade, Rebecca C.; Fiedler, Tomas (Journal of Biological Chemistry, 2013)

TRAPP: A Tool for Analysis of Transient Binding Pockets in Proteins - Kokh, Daria; Richter, Stefan; Henrich, Stefan; Czodrowski, Paul; Rippmann, Friedrich; Wade, Rebecca C. (Journal of Chemical Information and Modeling, 2013)

The Shape of Protein Crowders is a Major Determinant of Protein Diffusion - Balbo, Jessica; Mereghetti, Paolo; Herten, Dirk-Peter; Wade, Rebecca C. (Biophysical Journal, 2013)

Brownian dynamics simulation of protein diffusion in crowded environments - Mereghetti, Paolo; Wade, Rebecca C. (2013)

Conformational diversity and ligand tunnels of mammalian cytochrome P450s - Yu, Xiaofeng; Cojocaru, Vlad; Wade, Rebecca C. (Biotechnology and Applied Biochemistry, 2013)

Translational repression of thymidylate synthase by targeting its mRNA - Garg, Divita; Beribisky, Alexander V.; Ponterini, Glauco; Ligabue, Alessio; Marverti, Gaetano; Martello, Andrea; Costi, M. Paola; Sattler, Michael; Wade, Rebecca C. (Nucleic Acids Research, 2013)

Treating Conformational Flexibility in Protein-Protein Docking - Berynskyy, Mykhaylo; Wade, Rebecca C. (Current Physical Chemistry, 2013)

Ligand-based discovery of N-(1,3-dioxo-1H,3H-benzo[de]isochromen-5-yl)-carboxamide and sulfonamide derivatives as thymidylate synthase A inhibitors - Ferrari, Stefania; Ingrami, Marco; Soragni, Fabrizia; Wade, Rebecca C.; Costi, M. Paola (Bioorganic & Medicinal Chemistry Letters, 2013)

A tightly regulated molecular toggle controls AAA+ disaggregase - Oguchi, Yuki; Kummer, Eva; Seyffer, Fabian; Berynskyy, Mykhaylo; Anstett, Benjamin; Zahn, Regina; Wade, Rebecca C.; Mogk, Axel; Bukau, Bernd (Nature Structural & Molecular Biology, 2012)

Docking of Ubiquitin to Gold Nanoparticles - Brancolini, Giorgia; Kokh, Daria; Calzolai, Luigi; Wade, Rebecca C.; Corni, Stefano (ACS Nano, 2012)

Atomic Detail Brownian Dynamics Simulations of Concentrated Protein Solutions with a Mean Field Treatment of Hydrodynamic Interactions - Mereghetti, Paolo; Wade, Rebecca C. (The Journal of Physical Chemistry B, 2012)

A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB - Biedermannová, Lada; Prokop, Zbyněk; Gora, Artur; Chovancová, Eva; Kovács, Mihály; Damborský, Jiří; Wade, Rebecca C. (Journal of Biological Chemistry, 2012)

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity - Stein, Matthias; Pilli, Manohar; Bernauer, Sabine; Habermann, Bianca H.; Zerial, Marino; Wade, Rebecca C. (PLoS ONE, 2012)

Allosterically Gated Enzyme Dynamics in the Cysteine Synthase Complex Regulate Cysteine Biosynthesis in Arabidopsis thaliana - Feldman-Salit, Anna; Wirtz, Markus; Lenherr, Esther D.; Throm, Christian; Hothorn, Michael; Scheffzek, Klaus; Hell, Rüdiger; Wade, Rebecca C. (Structure, 2012)

Multiple, Ligand-dependent Routes from the Active Site of Cytochrome P450 2C9 - Cojocaru, Vlad; J. Winn, Peter; Wade, Rebecca C. (Current Drug Metabolism, 2012)

Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase - Cardinale, D.; Guaitoli, G.; Tondi, D.; Luciani, R.; Henrich, S.; Salo-Ahen, O. M. H.; Ferrari, S.; Marverti, G.; Guerrieri, D.; Ligabue, A.; Frassineti, C.; Pozzi, C.; et al. (Proceedings of the National Academy of Sciences, 2011)

Structure and Dynamics of the Membrane-Bound Cytochrome P450 2C9 - Cojocaru, Vlad; Balali-Mood, Kia; Sansom, Mark S. P.; Wade, Rebecca C. (PLoS Computational Biology, 2011)

The active-inactive transition of human thymidylate synthase: Targeted molecular dynamics simulations - Salo-Ahen, Outi M. H.; Wade, Rebecca C. (Proteins: Structure, Function, and Bioinformatics, 2011)

Diffusion of hydrophobin proteins in solution and interactions with a graphite surface - Mereghetti, Paolo; Wade, Rebecca C. (BMC Biophysics, 2011)

Structural Basis for the Varying Propensities of Different Amino Acids To Adopt the Collagen Conformation - S. Sundar, Raman; Gopalakrishnan, R.; Wade, Rebecca C.; Subramanian, V. (The Journal of Physical Chemistry B, 2011)

Receptor flexibility in small-molecule docking calculations - Kokh, Daria; Wade, Rebecca C.; Wenzel, Wolfgang (Wiley Interdisciplinary Reviews: Computational Molecular Science, 2011)

Diffusion and association processes in biological systems: theory, computation and experiment - Mereghetti, Paolo; Kokh, Daria; McCammon, J Andrew; Wade, Rebecca C. (BMC Biophysics, 2011)

On the structure and dynamics of the complex of the nucleosome and the linker histone - Pachov, Georgi V.; Gabdoulline, Razif R.; Wade, Rebecca C. (Nucleic Acids Research, 2011)

Virtual Screening Identification of Nonfolate Compounds, Including a CNS Drug, as Antiparasitic Agents Inhibiting Pteridine Reductase - Ferrari, Stefania; Morandi, Federica; Motiejunas, Domantas; Nerini, Erika; Henrich, Stefan; Luciani, Rosaria; Venturelli, Alberto; Lazzari, Sandra; Calò, Samuele; Gupta, Shreedhara; Hannaert, Veronique; Michels, Paul A. M.; et al. (Journal of Medicinal Chemistry, 2011)

A Quantitative, Real-Time Assessment of Binding of Peptides and Proteins to Gold Surfaces - Cohavi, Ori; Reichmann, Dana; Abramovich, Renne; Tesler, Alexander B.; Bellapadrona, Giuliano; Kokh, Daria; Wade, Rebecca C.; Vaskevich, Alexander; Rubinstein, Israel; Schreiber, Gideon (Chemistry - A European Journal, 2011)

Katalytische Wasserstofferzeugung an einem einkernigen Eisen(II)-Carbonylkomplex als kleinstes funktionelles Modell für das aktive Zentrum von [FeFe]-Hydrogenasen - Kaur-Ghumaan, Sandeep; Schwartz, Lennart; Lomoth, Reiner; Stein, Matthias; Ott, Sascha (Angewandte Chemie, 2010)

Catalytic Hydrogen Evolution from Mononuclear Iron(II) Carbonyl Complexes as Minimal Functional Models of the [FeFe] Hydrogenase Active Site - Kaur-Ghumaan, Sandeep; Schwartz, Lennart; Lomoth, Reiner; Stein, Matthias; Ott, Sascha (Angewandte Chemie International Edition, 2010)

Protein-Protein Complex Formation Affects the Ni-Fe and Fe-S Centers in the H2-Sensing Regulatory Hydrogenase from Ralstonia eutropha H16 - Löscher, Simone; Gebler, Antje; Stein, Matthias; Sanganas, Oliver; Buhrke, Thorsten; Zebger, Ingo; Dau, Holger; Friedrich, Bärbel; Lenz, Oliver; Haumann, Michael (ChemPhysChem, 2010)

Structure and Function of the Hetero-oligomeric Cysteine Synthase Complex in Plants - Wirtz, Markus; Birke, Hannah; Heeg, Corinna; Müller, Christopher; Hosp, Fabian; Throm, Christian; König, Stephan; Feldman-Salit, Anna; Rippe, Karsten; Petersen, Gabriele; Wade, Rebecca C.; Rybin, Vladimir; et al. (Journal of Biological Chemistry, 2010)

Brownian Dynamics Simulation of Protein Solutions: Structural and Dynamical Properties - Mereghetti, Paolo; Gabdoulline, Razif R.; Wade, Rebecca C. (Biophysical Journal, 2010)

Novel Approaches for Targeting Thymidylate Synthase To Overcome the Resistance and Toxicity of Anticancer Drugs - Garg, Divita; Henrich, Stefan; Salo-Ahen, Outi M. H.; Myllykallio, Hannu; Costi, Maria P.; Wade, Rebecca C. (Journal of Medicinal Chemistry, 2010)

Biochemical network-based drug-target prediction - Klipp, Edda; Wade, Rebecca C.; Kummer, Ursula (Current Opinion in Biotechnology, 2010)

ProMetCS: An Atomistic Force Field for Modeling Protein−Metal Surface Interactions in a Continuum Aqueous Solvent - Kokh, Daria; Corni, Stefano; Winn, Peter J.; Hoefling, Martin; Gottschalk, Kay E.; Wade, Rebecca C. (Journal of Chemical Theory and Computation, 2010)

Visualization of macromolecular structures - O'Donoghue, Seán I; Goodsell, David S; Frangakis, Achilleas S; Jossinet, Fabrice; Laskowski, Roman A; Nilges, Michael; Saibil, Helen R; Schafferhans, Andrea; Wade, Rebecca C.; Westhof, Eric; Olson, Arthur J (Nature Methods, 2010)

Design and characterization of a mutation outside the active site of human thymidylate synthase that affects ligand binding - Cardinale, D.; Salo-Ahen, O.M.H.; Guaitoli, G.; Ferrari, S.; Venturelli, A.; Franchini, S.; Battini, R.; Ponterini, G.; Wade, Rebecca C.; Costi, M.P. (Protein Engineering, Design and Selection, 2010)

Cross-species analysis of the glycolytic pathway by comparison of molecular interaction fields - Stein, Matthias; Gabdoulline, Razif R.; Wade, Rebecca C. (Mol. BioSyst., 2009)

Kinetics of Biomacromolecular Complex Formation: Theory and Experiment - Pachov, Georgi V.; Gabdoulline, Razif R.; Wade, Rebecca C. (Protein-Protein Complexes, 2010)

Comparative binding energy analysis for binding affinity and target selectivity prediction - Henrich, Stefan; Feierberg, Isabella; Wang, Ting; Blomberg, Niklas; Wade, Rebecca C. (Proteins: Structure, Function, and Bioinformatics, 2010)

MetaPocket: A Meta Approach to Improve Protein Ligand Binding Site Prediction - Huang, Bingding (OMICS: A Journal of Integrative Biology, 2009)

Design, Synthesis, and Biological Evaluation of Levoglucosenone-Derived Ras Activation Inhibitors - Müller, Christian; Gomez-Zurita Frau, Maria Antonia; Ballinari, Dario; Colombo, Sonia; Bitto, Alessandro; Martegani, Enzo; Airoldi, Cristina; van Neuren, Anske Stephanie; Stein, Matthias; Weiser, Jörg; Battistini, Carlo; Peri, Francesco (ChemMedChem, 2009)

(I,0) Mixed-Valence State of a Diiron Complex with Pertinence to the [FeFe]-Hydrogenase Active Site: An IR, EPR, and Computational Study - Singh, Pradyumna S.; Rudbeck, Hans Christian; Huang, Ping; Ezzaher, Salah; Eriksson, Lars; Stein, Matthias; Ott, Sascha; Lomoth, Reiner (Inorganic Chemistry, 2009)

Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate - Pavlova, Martina; Klvana, Martin; Prokop, Zbynek; Chaloupkova, Radka; Banas, Pavel; Otyepka, Michal; Wade, Rebecca C.; Tsuda, Masataka; Nagata, Yuji; Damborsky, Jiri (Nature Chemical Biology, 2009)

Pathways and Mechanisms for Product Release in the Engineered Haloalkane Dehalogenases Explored Using Classical and Random Acceleration Molecular Dynamics Simulations - Klvana, Martin; Pavlova, Martina; Koudelakova, Tana; Chaloupkova, Radka; Dvorak, Pavel; Prokop, Zbynek; Stsiapanava, Alena; Kuty, Michal; Kuta-Smatanova, Ivana; Dohnalek, Jan; Kulhanek, Petr; Wade, Rebecca C.; et al. (Journal of Molecular Biology, 2009)

On the Contributions of Diffusion and Thermal Activation to Electron Transfer between Phormidium laminosum Plastocyanin and Cytochrome f: Brownian Dynamics Simulations with Explicit Modeling of Nonpolar Desolvation Interactions and Electron Transfer Events - Gabdoulline, Razif R.; Wade, Rebecca C. (Journal of the American Chemical Society, 2009)

Computational Simulations of Protein– Protein and Protein– Nucleic Acid Association - Pachov, Georgi V.; Gabdoulline, Razif R.; Wade, Rebecca C. (2009)

Docking of a Linker Histone to The Nucleosome With Flexible Linker DNAs - Pachov, Georgi V.; Wade, Rebecca C. (Biophysical Journal, 2009)

Modeling of Protein Adsorption on a Metal Surface: Brownian Dynamics Simulations - Kokh, Daria; Huang, Bingding; Wade, Rebecca C.; Winn, Peter J. (Biophysical Journal, 2009)

A Mechanistic Model of the Cysteine Synthase Complex - Feldman-Salit, Anna; Wirtz, Markus; Hell, Ruediger; Wade, Rebecca C. (Journal of Molecular Biology, 2009)

CB Receptor Ligands from Plants - Bauer, Rudolf; Woelkart, Karin; Salo-Ahen, Outi (Current Topics in Medicinal Chemistry, 2008)

Editorial: The Medicinal Chemistry of Agents Targeting the Endogenous Cannabinoid System - Salo-Ahen, Outi (Current Topics in Medicinal Chemistry, 2008)

The acidic, glutamine-rich Mpn474 protein of Mycoplasma pneumoniae is surface exposed and covers the complete cell - Hegermann, Jan; Halbedel, Sven; Dumke, Roger; Regula, Jörg; Gabdoulline, Razif R.; Mayer, Frank; Stülke, Jörg; Herrmann, Richard (Microbiology, 2008)

webPIPSA: a web server for the comparison of protein interaction properties - Richter, Stefan; Wenzel, A.; Stein, M.; Gabdoulline, R. R.; Wade, Rebecca C. (Nucleic Acids Research, 2008)

SYCAMORE--a systems biology computational analysis and modeling research environment - Weidemann, Andreas; Richter, Stefan; Stein, M.; Sahle, S.; Gauges, R.; Gabdoulline, R.; Surovtsova, I.; Semmelrock, N.; Besson, B.; Rojas, I.; Wade, Rebecca C.; Kummer, U. (Bioinformatics, 2008)

Heterodimer formation of wild-type and amyotrophic lateral sclerosis-causing mutant Cu/Zn-superoxide dismutase induces toxicity independent of protein aggregation - Witan, Heidrun; Kern, Andreas; Koziollek-Drechsler, Ingrid; Wade, Rebecca C.; Behl, Christian; Clement, Albrecht M. (Human Molecular Genetics, 2008)

Protein-protein docking by simulating the process of association subject to biochemical constraints - Motiejunas, Domantas; Gabdoulline, Razif; Wang, Ting; Feldman-Salit, Anna; Johann, Tim; Winn, Peter J.; Wade, Rebecca C. (Proteins: Structure, Function, and Bioinformatics, 2008)

Calculating enzyme kinetic parameters from protein structures - Stein, Matthias; Gabdoulline, Razif R.; Wade, Rebecca C. (Biochemical Society Transactions, 2008)

Mechanism of Auxin Interaction with Auxin Binding Protein (ABP1): A Molecular Dynamics Simulation Study - Bertoša, Branimir; Kojić-Prodić, Biserka; Wade, Rebecca C.; Tomić, Sanja (Biophysical Journal, 2008)

On the use of PIPSA to Guide Target-Selective Drug Design - Henrich, Stefan; Richter, Stefan; Wade, Rebecca C. (ChemMedChem, 2008)

Ligand versus Metal Protonation of an Iron Hydrogenase Active Site Mimic - Eilers, Gerriet; Schwartz, Lennart; Stein, Matthias; Zampella, Giuseppe; de Gioia, Luca; Ott, Sascha; Lomoth, Reiner (Chemistry - A European Journal, 2007)

Facilitated Hydride Binding in an Fe−Fe Hydrogenase Active−Site Biomimic Revealed by X-ray Absorption Spectroscopy and DFT Calculations - Löscher, Simone; Schwartz, Lennart; Stein, Matthias; Ott, Sascha; Haumann, Michael (Inorganic Chemistry, 2007)

qPIPSA: Relating enzymatic kinetic parameters and interaction fields - Gabdoulline, Razif R; Stein, Matthias; Wade, Rebecca C. (BMC Bioinformatics, 2007)

Bridging from molecular simulation to biochemical networks - Stein, Matthias; Gabdoulline, Razif R; Wade, Rebecca C. (Current Opinion in Structural Biology, 2007)

Exploring biomolecular recognition by modelling and simulation - Wade, Rebecca C. (2007)

Simulation of linker histone-chromatin interactions - Pachov, Georgi; Gabdoulline, Razif R.; Wade, Rebecca C. (2007)

On the Use of Elevated Temperature in Simulations To Study Protein Unfolding Mechanisms - Wang, Ting; Wade, Rebecca C. (Journal of Chemical Theory and Computation, 2007)

Structural and electrostatic properties of ubiquitination and related pathways. - Winn, Peter J.; Zahran, Mai; Battey, James N.D.; Zhou, Yanxiang; Wade, Rebecca C.; Banerjee, Amit (Frontiers in Bioscience, 2007)

COMBINE analysis of the specificity of binding of Ras proteins to their effectors - Tomić, Sanja; Bertoša, Branimir; Wang, Ting; Wade, Rebecca C. (Proteins: Structure, Function, and Bioinformatics, 2007)

Comparisons of the protein electrostatic potentials as a means to understanding function - .Winn, Peter J; Zahran, Mai; Wade, Rebecca C. (2007)

FTIR studies of the redox partner interaction in cytochrome P450: The Pdx–P450cam couple - Karyakin, Andrey; Motiejunas, Domantas; Wade, Rebecca C.; Jung, Christiane (Biochimica et Biophysica Acta (BBA) - General Subjects, 2007)

The estimation of kinetic parameters in systems biology by comparing molecular interaction fields of enzymes. - Stein, Matthias; Gabdoulline, Razif R.; Besson, Bruno; Wade, Rebecca C. (2007)

The ins and outs of cytochrome P450s - Cojocaru, Vlad; Winn, Peter J.; Wade, Rebecca C. (Biochimica et Biophysica Acta (BBA) - General Subjects, 2007)

Characterization of protein-binding sites and ligands using molecular interaction fields. - Cruciani, Gabriele; Carosati, Emanuele; Wade, Rebecca C.; Baroni, Massimo (2007)

Katalytische Wasserstofferzeugung an einem einkernigen Eisen(II)- Carbonylkomplex als kleinstes funktionelles Modell fuer das aktive Zentrum von [FeFe]-Hydrogenasen - Kaur-Ghumaan, Sandeep; Schwartz, Lennart; Lomoth, Reiner; Stein, Matthias; Ott, Andreas (Angew. Chem., 2010)

Protein-protein complex formation affects the Ni-Fe and Fe-S centers in the H2-sensing regulatory hydrogenase from Ralstonia eutropha H16. - Löscher, Simone; Gebler, Antje; Stein, Matthias; Sanganas, Oliver; Buhrke, Thorsten; Zebger, Ingo; Dau, Holger; Friedrich, Bärbel; Lenz, Oliver; Haumann, Michael (Chem. Phys. Chem., 2010)

ProMetCS: An Atomistic Force Field for Modeling Protein-Metal Surface Interactions in a Continuum Aqueous Solvent - Kokh, Daria; Corni, Stefano; Winn, Peter J.; Hoefling, Martin; Gottschalk, Kay E.; Wade, Rebecca C. (J. Chem. Theory Comput., 2010)

Foreword Preface to the JMR Special Issue on ‘Dynamic Aspects of Molecular Recognition’ - Michielin, Olivier; Wade, Rebecca C. (Journal of Molecular Recognition, 2010)

Homodimeric Enzymes as Drug Targets - Cardinale, D.; Salo-Ahen, O.M.H.; Guaitoli, G.; Ferrari, S.; Venturelli, A.; Franchini, S.; Battini, R.; Ponterini, G.; Wade, Rebecca C.; Costi, M.P. (Curr. Med. Chem., 2010)

On the contributions of diffusion and thermal activation to electron transfer between Phormidium laminosum plastocyanin and cytochrome f: Brownian dynamics simulations with explicit modeling of nonpolar desolvation interactions and electron transfer events. - Gabdoulline, Razif R.; Wade, Rebecca C. (J. Am. Chem. Soc., 2009)

Computational Simulations of Protein-Protein and Protein-Nucleic Acid Association. - Pachov, Georgi V.; Gabdoulline, Razif R.; Wade, Rebecca C. (In " Computational Protein-Protein Interactions", Eds. R. Nussinov and G. Schreiber, Taylor and Francis Group LLC, Boca Raton, 2009)

Mechanism of auxin interaction with auxin binding protein (ABP1): a molecular dynamics simulation study - Bertoša, Branimir; Kojić-Prodić, Biserka; Wade, Rebecca C.; Tomić, Sanja (Biophys. J., 2008)

Structural and electrostatic properties of ubiquitination and related pathways - Winn, Peter J.; Zahran, Mai; Battey, James N.D.; Zhou, Yanxiang; Wade, Rebecca C.; Banerjee, Amit (Frontiers in Bioscience, 2007)

Integrating Structural and Kinetic Enzymatic Information in Systems Biology - Stein, Matthias; Gabdoulline, Razif R.; Wade, Rebecca C. (2006)

Molecular Docking - K., Schleinkofer; T., Wang; Wade, Rebecca C. (2006)

ProSAT2-Protein Structure Annotation Server - Gabdoulline, R. R.; Ulbrich, S.; Richter, Stefan; Wade, Rebecca C. (Nucl. Acids. Res., 2006)

Comparison of the binding and reactivity of plant and mammalian peroxidases to indole derivatives by computational docking - Hallingbäck, Henrik R.; Gabdoulline, Razif R.; Wade, Rebecca C. (Biochemistry, 2006)

Diffusional encounter of barnase and barstar - Spaar, Alexander; Dammer, Christian; Gabdoulline, Razif R.; Wade, Rebecca C.; Helms, Volkhard (Biophys. J., 2006)

Force Field Effects on a beta-sheet Protein Domain Structure in Thermal Unfolding Simulations - Wang, Ting; Wade, Rebecca C. (J. Chem. Theory Comput., 2006)

Use of Vibrational Spectroscopy to Study Protein and DNA Structure, Hydration, and Binding of Biomolecules: A Combined Theoretical and Experimental Approach - Jalkanen, K. J.; Würtz Jürgensen, V.; Claussen, A.; Rahim, A.; Jensen, G. M.; Wade, Rebecca C.; Nardi, F.; Jung, C.; Degtyarenko, I. M.; Nieminen, R. M.; Herrmann, F.; Knapp-Mohammady, M.; et al. (Intl. J. Quant. Chem., 2006)

Multiple molecular recognition mechanisms. Cytochrome P450–A case study - Wade, Rebecca C.; Motiejunas, Domantas; Schleinkofer, Karin; Sudarko, Peter J. Winn; Banerjee, Amit; Kariakin, Andrei; Jung, Christiane (Biochimica et Biophysica Acta, 2005)

Calculation and Application of Molecular Interaction Fields - Wade, Rebecca C. (2005)

Pushing the limits: Editorial overview - McCammon, J Andrew; Wade, Rebecca C. (Curr. Opin. Struct. Biol., 2005)

Do mammalian cytochrome P450s show multiple ligand access pathways and ligand channelling? - Schleinkofer, Karin; Sudarko, Peter J. Winn; Lüdemann, Susanna K.; Wade, Rebecca C. (EMBO Reports, 2005)

Recognition Highlights and Commentaries - Wade, Rebecca C. (J. Mol. Recognit., 2005)

Quantitative Analysis of Substrate Specificity of Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26 - Kmunícek, Jan; Hynková, Kamila; Jedlicka, Tomás; Nagata, Yuji; Negri, Ana; Gago, Federico; Wade, Rebecca C.; Damborský, Jirí (Biochemistry, 2005)

Issues in High-Throughput Comparative Modelling: A Case Study Using the Ubiquitin E2 Conjugating Enzymes - Winn, Peter J.; Battey, James N.; Schleinkofer, Karin; Banerjee, Amit; Wade, Rebecca C. (Proteins, 2005)

The Impact of Protein Flexibility on Protein-protein Docking - Ehrlich, Lutz P.; Nilges, Michael; Wade, Rebecca C. (Proteins, 2005)

Using 3D protein structures to derive 3D-QSARs - Wade, Rebecca C.; Henrich, Stefan; Wang, Ting (Drug Discovery Today: Technologies, 2004)

Comparative Structural and Energetic Analysis of WW Domain-Peptide Interactions - Schleinkofer, Karin; Wiedemann, Urs; Otte, Livia; Wang, Ting; Krause, Gerd; Oschkinat, Hartmut; Wade, Rebecca C. (J. Mol. Biol., 2004)

Determinants of Functionality in the Ubiquitin Conjugating Enzyme Family - Winn, Peter J.; Religa, Tomasz L.; Battey, James N.D.; Banerjee, Amit; Wade, Rebecca C. (Structure, 2004)

How Optimal are the Binding Energetics of Barnase and Barstar? - Wang, Ting; Tomic, Sanja; Gabdoulline, Razif R.; Wade, Rebecca C. (Biophys. J., 2004)

Computational approaches to structural and functional analysis of plastocyanin and other blue copper proteins - De Rienzo, F.; Gabdoulline, R. R.; Wade, Rebecca C.; Sola, M.; Menziani, M. C. (Cell Mol. Life Sci, 2004)

A survey of active site access channels in cytochromes P450 - Wade, Rebecca C.; Winn, Peter J; Schlichting, Ilme; Sudarko, (J. Inorg. Biochem., 2004)

Rational Re-design of Haloalkane Dehalogenases Guided by Comparative Binding Energy Analysis - Damborsky, Jiri; Kmunicek, Jan; Jedlicka, Tomas; Luengo, Santos; Gago, Federico; Ortiz, Angel R.; Wade, Rebecca C. (2004)