نتایج جستجو برای: binding pocket

تعداد نتایج: 429861  

Journal: :Proceedings of the National Academy of Sciences 2003

2016
Bin Peng Yi‐Jun Gu Ying Wang Fan‐Fan Cao Xue Zhang Deng‐Hai Zhang Jian Hou

Celastrol, a natural compound derived from the Chinese herb Tripterygium wilfordii Hook F, has been proven to inhibit heat shock protein 90 (HSP90) activity and has attracted much attention because of its promising effects in cancer treatment and in ameliorating degenerative neuron diseases. However, the HSP90 structure involved in celastrol interaction is not known. Here, we report a novel cel...

Journal: :Biochimica et biophysica acta 2012
Dabo Pan Weiwei Xue Wenqi Zhang Huanxiang Liu Xiaojun Yao

BACKGROUND ITMN-191 (RG7227, Danoprevir), as a potential inhibitor of the NS3/4A protease of hepatitis C virus, has been in phase 2 clinical trial. Unfortunately, several ITMN-191 resistance mutants including R155K, A156V, and D168A/E have been identified. METHODS Molecular dynamics simulation, binding free energy calculation and per-residue energy decomposition were employed to explore the b...

Journal: :Molecular pharmacology 2015
Maoqing Dong Ashton M Vattelana Polo C-H Lam Andrew J Orry Ruben Abagyan Arthur Christopoulos Patrick M Sexton David R Haines Laurence J Miller

Understanding the molecular basis of ligand binding to receptors provides insights useful for rational drug design. This work describes development of a new antagonist radioligand of the type 1 cholecystokinin receptor (CCK1R), (2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-l-H-indole-3-propanoate (T-0632), and exploration of the molecular basis of its binding. ...

2008
Susanne Eyrisch Volkhard Helms

The in-silico design of ligands binding to the protein surface instead of deep binding pockets is still a great challenge. Often no appropriate binding pockets are available in the apo experimental structures and standard virtual screening techniques will fail. Here, we present two new algorithms for designing tailored ligand binding pockets on the protein surface that account for protein backb...

2014
Travis S. Hughes Pankaj Kumar Giri Ian Mitchelle S. de Vera David P. Marciano Dana S. Kuruvilla Youseung Shin Anne-Laure Blayo Theodore M. Kamenecka Thomas P. Burris Patrick R. Griffin Douglas J. Kojetin

PPARγ is a target for insulin-sensitizing drugs such as glitazones, which improve plasma glucose maintenance in patients with diabetes. Synthetic ligands have been designed to mimic endogenous ligand binding to a canonical ligand-binding pocket to hyperactivate PPARγ. Here we reveal that synthetic PPARγ ligands also bind to an alternate site, leading to unique receptor conformational changes th...

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