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 semi-quantitatively.

References in corpus (3)

• Coupling hydrophobic, dispersion, and electrostatic contributions in continuum solvent models
• Coupling nonpolar and polar solvation free energies in implicit solvent models
• Application of the level-set method to the implicit solvation of nonpolar molecules

Cited by in corpus (4)

• Variational implicit-solvent predictions of the dry-wet transition pathways for ligand-receptor binding and unbinding kinetics
• How interface geometry dictates water's thermodynamic signature in hydrophobic association
• Affinity, Kinetics, and Pathways of Anisotropic Ligands Binding to Hydrophobic Model Pockets
• Binary Level Set Method for Variational Implicit Solvation Model