Dewetting-controlled binding of ligands to hydrophobic pockets.
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.
Setny
P
P
Department of Chemistry and Biochemistry, UC San Diego, La Jolla, California 92093, USA.
Wang
Z
Z
Cheng
L-T
LT
Li
B
B
McCammon
J A
JA
Dzubiella
J
J
D001665:Binding Sites; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*; D017155:Wettability
D008024:Ligands; D012997:Solvents; D014867:Water