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Simulating proteins at constant pH: An approach combining molecular dynamics and Monte Carlo simulation
Author(s) -
Bürgi Roland,
Kollman Peter A.,
van Gunsteren Wilfred F.
Publication year - 2002
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.10046
Subject(s) - protonation , monte carlo method , molecular dynamics , chemistry , lysozyme , titration , computational chemistry , statistical physics , thermodynamics , crystallography , physics , ion , mathematics , biochemistry , statistics , organic chemistry
For the structure and function of proteins, the pH of the solution is one of the determining parameters. Current molecular dynamics (MD) simulations account for the solution pH only in a limited way by keeping each titratable site in a chosen protonation state. We present an algorithm that generates trajectories at a Boltzmann distributed ensemble of protonation states by a combination of MD and Monte Carlo (MC) simulation. The algorithm is useful for pH‐dependent structural studies and to investigate in detail the titration behavior of proteins. The method is tested on the acidic residues of the protein hen egg white lysozyme. It is shown that small structural changes may have a big effect on the pK A values of titratable residues. Proteins 2002;47:469–480. © 2002 Wiley‐Liss, Inc.