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Dewetting-controlled binding of ligands to hydrophobic pockets.

ABSTRACT: We report on a combined atomistic molecular dynamics simulation and implicit solvent analysis of a generic hydrophobic pocket-ligand (host-guest) system. The approaching ligand induces complex wetting-dewetting transitions in the weakly solvated pocket. The transitions lead to bimodal solvent fluctuations which govern magnitude and range of the pocket-ligand attraction. A recently developed implicit water model, based on the minimization of a geometric functional, captures the sensitive aqueous interface response to the concave-convex pocket-ligand configuration semiquantitatively.

SUBMITTER: Setny P

PROVIDER: S-EPMC2832595 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Dewetting-controlled binding of ligands to hydrophobic pockets.

Setny P P Wang Z Z Cheng L-T LT Li B B McCammon J A JA Dzubiella J J

Physical review letters 20091030 18

We report on a combined atomistic molecular dynamics simulation and implicit solvent analysis of a generic hydrophobic pocket-ligand (host-guest) system. The approaching ligand induces complex wetting-dewetting transitions in the weakly solvated pocket. The transitions lead to bimodal solvent fluctuations which govern magnitude and range of the pocket-ligand attraction. A recently developed implicit water model, based on the minimization of a geometric functional, captures the sensitive aqueous ...[more]

PMID: 19905832

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