Multiple pH regime molecular dynamics simulation for pK calculations.

Ionisation equilibria in proteins are influenced by conformational flexibility, which can in principle be accounted for by molecular dynamics simulation. One problem in this method is the bias arising from the fixed protonation state during the simulation. Its effect is mostly exhibited when the ion...

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Autores principales:	Lennart Nilsson, Andrey Karshikoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e773806b6c04856ae9d4c05aae87b5d
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spelling	oai:doaj.org-article:1e773806b6c04856ae9d4c05aae87b5d2021-11-18T06:52:59ZMultiple pH regime molecular dynamics simulation for pK calculations.1932-620310.1371/journal.pone.0020116https://doaj.org/article/1e773806b6c04856ae9d4c05aae87b5d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21647418/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Ionisation equilibria in proteins are influenced by conformational flexibility, which can in principle be accounted for by molecular dynamics simulation. One problem in this method is the bias arising from the fixed protonation state during the simulation. Its effect is mostly exhibited when the ionisation behaviour of the titratable groups is extrapolated to pH regions where the predetermined protonation state of the protein may not be statistically relevant, leading to conformational sampling that is not representative of the true state. In this work we consider a simple approach which can essentially reduce this problem. Three molecular dynamics structure sets are generated, each with a different protonation state of the protein molecule expected to be relevant at three pH regions, and pK calculations from the three sets are combined to predict pK over the entire pH range of interest. This multiple pH molecular dynamics approach was tested on the GCN4 leucine zipper, a protein for which a full data set of experimental data is available. The pK values were predicted with a mean deviation from the experimental data of 0.29 pH units, and with a precision of 0.13 pH units, evaluated on the basis of equivalent sites in the dimeric GCN4 leucine zipper.Lennart NilssonAndrey KarshikoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20116 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lennart Nilsson Andrey Karshikoff Multiple pH regime molecular dynamics simulation for pK calculations.
description	Ionisation equilibria in proteins are influenced by conformational flexibility, which can in principle be accounted for by molecular dynamics simulation. One problem in this method is the bias arising from the fixed protonation state during the simulation. Its effect is mostly exhibited when the ionisation behaviour of the titratable groups is extrapolated to pH regions where the predetermined protonation state of the protein may not be statistically relevant, leading to conformational sampling that is not representative of the true state. In this work we consider a simple approach which can essentially reduce this problem. Three molecular dynamics structure sets are generated, each with a different protonation state of the protein molecule expected to be relevant at three pH regions, and pK calculations from the three sets are combined to predict pK over the entire pH range of interest. This multiple pH molecular dynamics approach was tested on the GCN4 leucine zipper, a protein for which a full data set of experimental data is available. The pK values were predicted with a mean deviation from the experimental data of 0.29 pH units, and with a precision of 0.13 pH units, evaluated on the basis of equivalent sites in the dimeric GCN4 leucine zipper.
format	article
author	Lennart Nilsson Andrey Karshikoff
author_facet	Lennart Nilsson Andrey Karshikoff
author_sort	Lennart Nilsson
title	Multiple pH regime molecular dynamics simulation for pK calculations.
title_short	Multiple pH regime molecular dynamics simulation for pK calculations.
title_full	Multiple pH regime molecular dynamics simulation for pK calculations.
title_fullStr	Multiple pH regime molecular dynamics simulation for pK calculations.
title_full_unstemmed	Multiple pH regime molecular dynamics simulation for pK calculations.
title_sort	multiple ph regime molecular dynamics simulation for pk calculations.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1e773806b6c04856ae9d4c05aae87b5d
work_keys_str_mv	AT lennartnilsson multiplephregimemoleculardynamicssimulationforpkcalculations AT andreykarshikoff multiplephregimemoleculardynamicssimulationforpkcalculations
_version_	1718424215284088832

Multiple pH regime molecular dynamics simulation for pK calculations.

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