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A fast and simple method to calculate protonation states in proteins
Author(s) -
Sandberg Lars,
Edholm Olle
Publication year - 1999
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/(sici)1097-0134(19990901)36:4<474::aid-prot12>3.0.co;2-v
Subject(s) - poisson–boltzmann equation , protonation , boltzmann constant , chemistry , statistical physics , dielectric , molecular dynamics , computational chemistry , monte carlo method , coupling constant , physics , thermodynamics , ion , quantum mechanics , mathematics , statistics , organic chemistry
A simple model for electrostatic interactions in proteins, based on a distance and position dependent screening of the electrostatic potential, is presented. It is applied in conjunction with a Monte Carlo algorithm to calculate p K α values of ionizable groups in proteins. The purpose is to furnish a simple, fast, and sufficiently accurate model to be incorporated into molecular dynamic simulations. This will allow for dynamic protonation calculations and for coupling between changes in structure and protonation state during the simulation. The best method of calculating protonation states available today is based on solving the linearized Poisson‐Boltzmann equation on a finite difference grid. However, this model consumes far too much computer time to be a practical alternative. Tests are reported for fixed structures on bacteriorhodopsin, lysozyme, myoglobin, and calbindin. The studies include comparisons with Poisson‐Boltzmann calculations with dielectric constants 4 and 20 inside the protein, a model with uniform dielectric constant 80 and distance‐dependent dielectric models. The accuracy is comparable to that of Poisson‐Boltzmann calculations with dielectric constant 20, and it is considerably better than that with ϵ = 4. The time to calculate the protonation at one p H value is at least 100 times less than that of a Poisson‐Boltzmann calculation. Proteins 1999;36:474–483. © 1999 Wiley‐Liss, Inc.