Balancing Solvation and Intramolecular Interactions: Toward a Consistent Generalized Born Force Field Export

@article{chen:06b, abstract = {PMID: 16536547 The efficient and accurate characterization of solvent effects is a key element in the theoretical and computational study of biological problems. Implicit solvent models, particularly generalized Born (GB) continuum electrostatics, have emerged as an attractive tool to study the structure and dynamics of biomolecules in various environments. Despite recent advances in this methodology, there remain limitations in the parametrization of many of these models. In the present work, we demonstrate that it is possible to achieve a balanced implicit solvent force field by further optimizing the input atomic radii in combination with adjusting the protein backbone torsional energetics. This parameter optimization is guided by the potentials of mean force (PMFs) between amino acid polar groups, calculated from explicit solvent free energy simulations, and by conformational equilibria of short peptides, obtained from extensive folding and unfolding replica exchange molecular dynamics (REX-MD) simulations. Through the application of this protocol, the delicate balance between the competing solvation forces and intramolecular forces appears to be better captured, and correct conformational equilibria for a range of both helical and beta-hairpin peptides are obtained. The same optimized force field also successfully folds both beta-hairpin trpzip2 and mini-protein Trp-Cage, indicating that it is quite robust. Such a balanced, physics-based force field will be highly applicable to a range of biological problems including protein folding and protein structural dynamics.}, address = {Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.}, author = {Chen, Jianhan and Im, Wonpil and Brooks, Charles L.}, citeulike-article-id = {608672}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja057216r}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja057216r}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16536547}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16536547}, day = {1}, doi = {10.1021/ja057216r}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {force-fields, generalized-born, interactions, solvation}, month = {March}, number = {11}, pages = {3728--3736}, posted-at = {2009-01-08 21:57:21}, priority = {0}, title = {Balancing Solvation and Intramolecular Interactions: Toward a Consistent Generalized Born Force Field}, url = {http://dx.doi.org/10.1021/ja057216r}, volume = {128}, year = {2006} }

TY - JOUR ID - chen:06b L3 - citeulike-article-id:608672 N2 - PMID: 16536547 The efficient and accurate characterization of solvent effects is a key element in the theoretical and computational study of biological problems. Implicit solvent models, particularly generalized Born (GB) continuum electrostatics, have emerged as an attractive tool to study the structure and dynamics of biomolecules in various environments. Despite recent advances in this methodology, there remain limitations in the parametrization of many of these models. In the present work, we demonstrate that it is possible to achieve a balanced implicit solvent force field by further optimizing the input atomic radii in combination with adjusting the protein backbone torsional energetics. This parameter optimization is guided by the potentials of mean force (PMFs) between amino acid polar groups, calculated from explicit solvent free energy simulations, and by conformational equilibria of short peptides, obtained from extensive folding and unfolding replica exchange molecular dynamics (REX-MD) simulations. Through the application of this protocol, the delicate balance between the competing solvation forces and intramolecular forces appears to be better captured, and correct conformational equilibria for a range of both helical and beta-hairpin peptides are obtained. The same optimized force field also successfully folds both beta-hairpin trpzip2 and mini-protein Trp-Cage, indicating that it is quite robust. Such a balanced, physics-based force field will be highly applicable to a range of biological problems including protein folding and protein structural dynamics. IS - 11 JF - Journal of the American Chemical Society SN - 0002-7863 AD - Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. EP - 3736 TI - Balancing Solvation and Intramolecular Interactions: Toward a Consistent Generalized Born Force Field VL - 128 SP - 3728 KW - force-fields KW - generalized-born KW - interactions KW - solvation AU - Chen, Jianhan AU - Im, Wonpil AU - Brooks, Charles PY - 2006/03/01/ UR - http://dx.doi.org/10.1021/ja057216r ER -