Hydrogen bonding penalty upon ligand binding.

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 pe...

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Autores principales:	Hongtao Zhao, Danzhi Huang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83d6805e84254319b283d33d762beb2a
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spelling	oai:doaj.org-article:83d6805e84254319b283d33d762beb2a2021-11-18T06:51:46ZHydrogen bonding penalty upon ligand binding.1932-620310.1371/journal.pone.0019923https://doaj.org/article/83d6805e84254319b283d33d762beb2a2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21698148/?tool=EBIhttps://doaj.org/toc/1932-6203Ligand 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.Hongtao ZhaoDanzhi HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e19923 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hongtao Zhao Danzhi Huang Hydrogen bonding penalty upon ligand binding.
description	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.
format	article
author	Hongtao Zhao Danzhi Huang
author_facet	Hongtao Zhao Danzhi Huang
author_sort	Hongtao Zhao
title	Hydrogen bonding penalty upon ligand binding.
title_short	Hydrogen bonding penalty upon ligand binding.
title_full	Hydrogen bonding penalty upon ligand binding.
title_fullStr	Hydrogen bonding penalty upon ligand binding.
title_full_unstemmed	Hydrogen bonding penalty upon ligand binding.
title_sort	hydrogen bonding penalty upon ligand binding.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/83d6805e84254319b283d33d762beb2a
work_keys_str_mv	AT hongtaozhao hydrogenbondingpenaltyuponligandbinding AT danzhihuang hydrogenbondingpenaltyuponligandbinding
_version_	1718424303907635200

Hydrogen bonding penalty upon ligand binding.

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