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Protein molecular dynamics with the generalized born/ACE solvent model
Author(s) -
Calimet Nicolas,
Schaefer Michael,
Simonson Thomas
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.1134
Subject(s) - molecular dynamics , dipole , chemistry , statistical physics , solvent , accessible surface area , computational chemistry , physics , materials science , chemical physics , organic chemistry
Implicit solvent models are increasingly important for the study of proteins in aqueous solution. Here, the generalized Born (GB) solvent polarization model as implemented in the analytical ACE potential [Schaefer and Karplus (1996) J Phys Chem 100:1578] is used to perform molecular dynamics simulations of two small, homologous proteins: the immunoglobulin‐binding domain of streptococcal protein G and the Ras binding domain of Raf. Several model parameterizations are compared through more than 60 ns of simulation. Results are compared with two simpler solvent models—an accessible surface area model and a distant‐dependent dielectric model, with finite‐difference Poisson calculations, with existing explicit solvent simulations, and with experimental data. The simpler models yield stable but distorted structures. The best GB/ACE implementation uses a set of atomic Voronoi volumes reported recently, obtained by averaging over a large database of crystallographic protein structures. A 20% reduction is applied to the volumes, compensating in an average sense for an excessive de‐screening of individual charges inherent in the ACE self‐energy and for an undersolvation of dipolar groups inherent in the GB screening function. This GB/ACE parameterization yields stable trajectories on the 0.5–1‐ns time scale that deviate moderately (∼1.5–2.5 Å) from the X‐ray structure, reproduce approximately the surface distribution of charged, polar, and hydrophobic groups, and reproduce accurately backbone flexibility as measured by amide NMR‐order parameters. Over longer time scales (1.5–3 ns), some of the protein G runs escape from the native energy basin and deviate strongly (3 Å) from the native structure. The conformations sampled during the transition out of the native energy basin are overstabilized by the GB/ACE solvation model, as compared with a numerical treatment of the full dielectric continuum model. Proteins 2001;45:144–158. © 2001 Wiley‐Liss, Inc.