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Optimizing the hydrogen‐bond network in Poisson–Boltzmann equation‐based p K a calculations
Author(s) -
Nielsen Jens E.,
Vriend Gerrit
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1053
Subject(s) - protonation , poisson–boltzmann equation , hydrogen bond , boltzmann constant , chemistry , bond length , poisson distribution , crystal (programming language) , computational chemistry , physics , statistical physics , thermodynamics , mathematics , molecule , crystallography , crystal structure , quantum mechanics , computer science , statistics , ion , programming language
Abstract p K a calculation methods that are based on finite difference solutions to the Poisson–Boltzmann equation (FDPB) require that energy calculations be performed for a large number of different protonation states of the protein. Normally, the differences between these protonation states are modeled by changing the charges on a few atoms, sometimes the differences are modeled by adding or removing hydrogens, and in a few cases the positions of these hydrogens are optimized locally. We present an FDPB‐based p K a calculation method in which the hydrogen‐bond network is globally optimized for every single protonation state used. This global optimization gives a significant improvement in the accuracy of calculated p K a values, especially for buried residues. It is also shown that large errors in calculated p K a values are often due to structural artifacts induced by crystal packing. Optimization of the force fields and parameters used in p K a calculations should therefore be performed with X‐ray structures that are corrected for crystal artifacts. Proteins 2001;43:403–412. © 2001 Wiley‐Liss, Inc.