title: Critical importance of length-scale dependence in implicit modeling of hydrophobic interactions.
abstract: The existence of length-scale dependence of hydrophobic solvation has important implications in the equilibrium of disordered, partially folded, and folded protein conformations. Neglecting this dependence, such as in popular solute surface-area based implicit solvent models with fixed surface tension coefficients, severely limits the ability to accurately model protein conformational equilibrium. We illustrate such fundamental limitations by examining the potentials of mean force of forming dimeric and trimeric nonpolar clusters and propose a new empirical model that effectively captures the context dependence of the local effective surface tension. Further optimization of the new model with other components of the implicit solvent force fields provides promise to significantly improve one's ability to simulate protein folding and conformational transitions. The existence of length-scale dependence of hydrophobic solvation has important implications in the equilibrium of disordered, partially folded, and folded protein conformations. Neglecting this dependence, such as in popular solute surface-area based implicit solvent models with fixed surface tension coefficients, severely limits the ability to accurately model protein conformational equilibrium. We illustrate such fundamental limitations by examining the potentials of mean force of forming dimeric and trimeric nonpolar clusters and propose a new empirical model that effectively captures the context dependence of the local effective surface tension. Further optimization of the new model with other components of the implicit solvent force fields provides promise to significantly improve one's ability to simulate protein folding and conformational transitions.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jianhan
authors.initials: J
authors.lastname: Chen
authors.forename: Charles L
authors.initials: CL
authors.lastname: Brooks
mesh_terms: D000465:Algorithms; D019281:Dimerization; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D010455:Peptides; D011506:Proteins