Publications

1291 Publications visible to you, out of a total of 1291

Abstract

Not specified

Authors: Hanno Schmidt, Katharina Mauer, Manuel Glaser, Bahram Sayyaf Dezfuli, Sören Lukas Hellmann, Ana Lúcia Silva Gomes, Falk Butter, Rebecca C. Wade, Thomas Hankeln, Holger Herlyn

Date Published: 1st Dec 2022

Publication Type: Journal

Abstract (Expand)

Von Willebrand disease (VWD) is a bleeding disorder with different levels of severity. VWD-associated mutations are located in the von Willebrand factor (VWF) gene, coding for the large multidomain plasma protein VWF with essential roles in hemostasis and thrombosis. On the one hand, a variety of mutations in the C-domains of VWF are associated with increased bleeding upon vascular injury. On the other hand, VWF gain-of-function (GOF) mutations in the C4 domain have recently been identified, which induce an increased risk of myocardial infarction. Mechanistic insights into how these mutations affect the molecular behavior of VWF are scarce and holistic approaches are challenging due to the multidomain and multimeric character of this large protein. Here, we determine the structure and dynamics of the C6 domain and the single nucleotide polymorphism (SNP) variant G2705R in C6 by combining nuclear magnetic resonance spectroscopy, molecular dynamics simulations and aggregometry. Our findings indicate that this mutation mostly destabilizes VWF by leading to a more pronounced hinging between both subdomains of C6. Hemostatic parameters of variant G2705R are close to normal under static conditions, but the missense mutation results in a gain-of-function under flow conditions, due to decreased VWF stem stability. Together with the fact that two C4 variants also exhibit GOF characteristics, our data underline the importance of the VWF stem region in VWF’s hemostatic activity and the risk of mutation-associated prothrombotic properties in VWF C-domain variants due to altered stem dynamics.

Authors: Po-Chia Chen, Fabian Kutzki, Angelika Mojzisch, Bernd Simon, Emma-Ruoqi Xu, Camilo Aponte-Santamaría, Kai Horny, Cy Jeffries, Reinhard Schneppenheim, Matthias Wilmanns, Maria A. Brehm, Frauke Gräter, Janosch Hennig

Date Published: 18th Nov 2022

Publication Type: Journal

Abstract (Expand)

Heteroatom-doped polyaromatic hydrocarbons (or nanographenes) are promising molecular electrocatalysts for the oxygen reduction reaction (ORR). Here, we use density functional theory to investigate the first step of the ORR pathway (chemisorption) for a set of molecules with experimentally determined catalytic activities. Weak chemisorptions are found only for negatively charged catalysts, and a strong correlation is observed between computed electron affinities and experimental catalytic activities for a range of B- and B,N-doped polyaromatic hydrocarbons. The electron affinity is put forward as a simple activity descriptor of charged (activated) catalysts on an electrode.

Authors: Christopher Ehlert, Anna Piras, Juliette Schleicher, Ganna Gryn'ova

Date Published: 14th Nov 2022

Publication Type: Journal

Abstract (Expand)

Molecular docking has traditionally mostly been employed in the field of protein- ligand binding. Here, we extend this method, in combination with DFT-level geometry optimizations, to locate guest molecules inside the pores of metal-organic frameworks. The position and nature of the guest molecules tune the physicochemical properties of the host-guest systems. Therefore, it is essential to be able to reliably locate them to rationally enhance the performance of the known metal-organic frameworks and facilitate new material discovery. The results obtained with this approach are compared to experimental data. We show that the presented method can, in general, accurately locate adsorption sites and structures of the host-guest complexes. We therefore propose our approach as a computational alternative when no experimental structures of guest-loaded MOFs are available. Additional information on the adsorption strength in the studied host-guest systems emerges from the computed interaction energies. Our findings provide the basis for other computational studies on MOF-guest systems and contribute to a better understanding of the structure-interaction-property interplay associated with them.

Authors: Michelle Ernst, Tomasz Poręba, Lars Gnägi, Ganna Gryn'ova

Date Published: 9th Nov 2022

Publication Type: Journal

Abstract

Not specified

Authors: Tilmann Gneiting, Daniel Wolffram, Johannes Resin, Kristof Kraus, Johannes Bracher, Timo Dimitriadis, Veit Hagenmeyer, Alexander I. Jordan, Sebastian Lerch, Kaleb Phipps, Melanie Schienle

Date Published: 1st Nov 2022

Publication Type: Journal

Abstract

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Authors: Johannes Bracher, Daniel Wolffram, Jannik Deuschel, Konstantin Görgen, Jakob L. Ketterer, Alexander Ullrich, Sam Abbott, Maria V. Barbarossa, Dimitris Bertsimas, Sangeeta Bhatia, Marcin Bodych, Nikos I. Bosse, Jan Pablo Burgard, Lauren Castro, Geoffrey Fairchild, Jochen Fiedler, Jan Fuhrmann, Sebastian Funk, Anna Gambin, Krzysztof Gogolewski, Stefan Heyder, Thomas Hotz, Yuri Kheifetz, Holger Kirsten, Tyll Krueger, Ekaterina Krymova, Neele Leithäuser, Michael L. Li, Jan H. Meinke, Błażej Miasojedow, Isaac J. Michaud, Jan Mohring, Pierre Nouvellet, Jedrzej M. Nowosielski, Tomasz Ożański, Maciej Radwan, Franciszek Rakowski, Markus Scholz, Saksham Soni, Ajitesh Srivastava, Tilmann Gneiting, Melanie Schienle

Date Published: 31st Oct 2022

Publication Type: Journal

Abstract

Not specified

Authors: Marcus Fabiano de Almeida Mendes, Marcelo de Souza Bragatte, Priscila Vianna, Martiela Vaz de Freitas, Ina Pöhner, Stefan Richter, Rebecca C. Wade, Francisco Mauro Salzano, Gustavo Fioravanti Vieira

Date Published: 28th Oct 2022

Publication Type: Journal

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