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Published year: 20185
The Evolution of Multiple Active Site Configurations in a Designed Enzyme

Abstract (Expand)

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.

Authors: Nan-Sook Hong, Dušan Petrović, Richmond Lee, Ganna Gryn’ova, Miha Purg, Jake Saunders, Paul Bauer, Paul D. Carr, Ching-Yeh Lin, Peter D. Mabbitt, William Zhang, Timothy Altamore, Chris Easton, Michelle L. Coote, Shina C. L. Kamerlin, Colin J. Jackson

Date Published: 1st Dec 2018

Publication Type: Journal

Read between the Molecules: Computational Insights into Organic Semiconductors

Abstract (Expand)

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.

Authors: Ganna Gryn’ova, Kun-Han Lin, Clémence Corminboeuf

Date Published: 5th Nov 2018

Publication Type: Journal

Noncovalent Molecular Electronics

Abstract (Expand)

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.

Authors: G. Gryn’ova, C. Corminboeuf

Date Published: 17th Apr 2018

Publication Type: Journal

Steric “Attraction”: Not by Dispersion Alone

Abstract (Expand)

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.

Authors: Ganna Gryn’ova, Clémence Corminboeuf

Date Published: 2018

Publication Type: Journal

Fine-Tuned Organic Photoredox Catalysts for Fragmentation-Alkynylation Cascades of Cyclic Oxime Ethers

Abstract (Expand)

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.

Authors: Franck Le Vaillant, Marion Garreau, Stefano Nicolai, Ganna Gryn'ova, Clemence Corminboeuf, Jerome Waser

Date Published: 2018

Publication Type: Journal

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