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452 Publications visible to you, out of a total of 452
A novel method to treat gated protein-ligand binding via on-the-fly conformational updates within rigid body BD simulations

Abstract

Not specified

Author: Patrick Friedrich

Date Published: 2018

Publication Type: Master's Thesis

A computational approach to decipher chromatosome structure determinants

Abstract

Not specified

Author: Mehmet Ali Öztuerk

Date Published: 2018

Publication Type: Doctoral Thesis

Modelling of Neurotrophin Receptors

Abstract

Not specified

Author: Jan-Niklas Dohrke

Date Published: 2018

Publication Type: Bachelor's Thesis

Protein conformational flexibility modulates kinetics and thermodynamics of drug binding

Abstract (Expand)

Structure-based drug design has often been restricted by the rather static picture of protein–ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility …y in biomolecular recognition. Here we report a detailed experimental and computational study of the drug target, human heat shock protein 90, to explore the contribution of protein dynamics to the binding thermodynamics and kinetics of drug-like compounds. We observe that their binding properties depend on whether the protein has a loop or a helical conformation in the binding site of the ligand-bound state. Compounds bound to the helical conformation display slow association and dissociation rates, high-affinity and high cellular efficacy, and predominantly entropically driven binding. An important entropic contribution comes from the greater flexibility of the helical relative to the loop conformation in the ligand-bound state. This unusual mechanism suggests increasing target flexibility in the bound state by ligand design as a new strategy for drug discovery.

Authors: M. Amaral, D. B. Kokh, J. Bomke, A. Wegener, H. P. Buchstaller, H. M. Eggenweiler, P. Matias, C. Sirrenberg, R. C. Wade, M. Frech

Date Published: 1st Dec 2017

Publication Type: Journal

Early career researchers want Open Science

Abstract (Expand)

Open Science is encouraged by the European Union and many other political and scientific institutions. However, scientific practice is proving slow to change. We propose, as early career researchers, … that it is our task to change scientific research into open scientific research and commit to Open Science principles.

Authors: Andrea Farnham, Christoph Kurz, Mehmet Ali Öztürk, Monica Solbiati, Oona Myllyntaus, Jordy Meekes, Tra My Pham, Clara Paz, Magda Langiewicz, Sophie Andrews, Liisa Kanninen, Chantal Agbemabiese, Arzu Tugce Guler, Jeffrey Durieux, Sarah Jasim, Olivia Viessmann, Stefano Frattini, Danagul Yembergenova, Carla Marin Benito, Marion Porte, Anaïs Grangeray-Vilmint, Rafael Prieto Curiel, Carin Rehncrona, Tareq Malas, Flavia Esposito, Kristina Hettne

Date Published: 1st Dec 2017

Publication Type: Journal

Comparative mapping of on-targets and off-targets for the discovery of anti-trypanosomatid folate pathway inhibitors

Abstract

Not specified

Authors: Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C. Wade

Date Published: 1st Dec 2017

Publication Type: Journal

A novel homozygous ARL13B variant in patients with Joubert syndrome impairs its guanine nucleotide-exchange factor activity

Abstract (Expand)

ARL13B encodes for the ADP-ribosylation factor-like 13B GTPase, which is required for normal cilia structure and Sonic hedgehog (Shh) signaling. Disruptions in cilia structure or function lead to a … class of human disorders called ciliopathies. Joubert syndrome is characterized by a wide spectrum of symptoms, including a variable degree of intellectual disability, ataxia, and ocular abnormalities. Here we report a novel homozygous missense variant c.[223G>A] (p.(Gly75Arg) in the ARL13B gene, which was identified by whole-exome sequencing of a trio from a consanguineous family with multiple-affected individuals suffering from intellectual disability, ataxia, ocular defects, and epilepsy. The same variant was also identified in a second family. We saw a striking difference in the severity of ataxia between affected male and female individuals in both families. Both ARL13B and ARL13B-c.[223G>A] (p.(Gly75Arg) expression rescued the cilia length and Shh defects displayed by Arl13b hennin (null) cells, indicating that the variant did not disrupt either ARL13B function. In contrast, ARL13B-c.[223G>A] (p.(Gly75Arg) displayed a marked loss of ARL3 guanine nucleotide-exchange factor activity, with retention of its GTPase activities, highlighting the correlation between its loss of function as an ARL3 guanine nucleotide-exchange factor and Joubert syndrome.

Authors: Rafiullah Rafiullah, Alyssa B. Long, Anna A. Ivanova, Hazrat Ali, Simone Berkel, Ghulam Mustafa, Nagarajan Paramasivam, Matthias Schlesner, Stefan Wiemann, Rebecca C. Wade, Eugen Bolthauser, Martin Blum, Richard A. Kahn, Tamara Caspary, Gudrun A. Rappold

Date Published: 1st Dec 2017

Publication Type: Journal

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