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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48626

Zhao, H; Huang, D (2011). Hydrogen bonding penalty upon ligand binding. PLoS ONE, 6(6):e19923.

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Abstract

Ligand binding involves breakage of hydrogen bonds with water molecules and formation of new hydrogen bonds between protein and ligand. In this work, the change of hydrogen bonding energy in the binding process, namely hydrogen bonding penalty, is evaluated with a new method. The hydrogen bonding penalty can not only be used to filter unrealistic poses in docking, but also improve the accuracy of binding energy calculation. A new model integrated with hydrogen bonding penalty for free energy calculation gives a root mean square error of 0.7 kcal/mol on 74 inhibitors in the training set and of 1.1 kcal/mol on 64 inhibitors in the test set. Moreover, an application of hydrogen bonding penalty into a high throughput docking campaign for EphB4 inhibitors is presented, and remarkably, three novel scaffolds are discovered out of seven tested. The binding affinity and ligand efficiency of the most potent compound is about 300 nM and 0.35 kcal/mol per non-hydrogen atom, respectively.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
DDC:570 Life sciences; biology
Language:English
Date:2011
Deposited On:07 Jul 2011 09:12
Last Modified:27 Nov 2013 23:27
Publisher:Public Library of Science
ISSN:1932-6203
Publisher DOI:10.1371/journal.pone.0019923
PubMed ID:21698148
Citations:Web of Science®. Times Cited: 8
Google Scholar™
Scopus®. Citation Count: 9

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