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Development of the force field parameters for phosphoimidazole and phosphohistidine
Author(s) -
Kosinsky Yuri A.,
Volynsky Pavel E.,
Lagant Philippe,
Vergoten Gerard,
Suzuki EiIchiro,
Arseniev Alexander S.,
Efremov Roman G.
Publication year - 2004
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20055
Subject(s) - molecular dynamics , molecular mechanics , force field (fiction) , chemistry , computational chemistry , ab initio , moiety , chemical physics , physics , stereochemistry , quantum mechanics , organic chemistry
Phosphorylation of histidine‐containing proteins is a key step in the mechanism of many phosphate transfer enzymes (kinases, phosphatases) and is the first stage in a wide variety of signal transduction cascades in bacteria, yeast, higher plants, and mammals. Studies of structural and dynamical aspects of such enzymes in the phosphorylated intermediate states are important for understanding the intimate molecular mechanisms of their functioning. Such information may be obtained via molecular dynamics and/or docking simulations, but in this case appropriate force field parameters for phosphohistidine should be explicitly defined. In the present article we describe development of the GROMOS96 force field parameters for phosphoimidazole molecule—a realistic model of the phosphohistidine side chain. The parameterization is based on the results of ab initio quantum chemical calculations with subsequent refinement and testing using molecular mechanics and molecular dynamics simulations. The set of force constants and equilibrium geometry is employed to derive force field for the phosphohistidine moiety. Resulting parameters and topology are incorporated into the molecular modeling package GROMACS and used in molecular dynamics simulations of a phosphohistidine‐containing protein in explicit solvent. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1313–1321, 2004