BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Bo Li (University of California\, San Diego) DTSTART:20200603T150000Z DTEND:20200603T160000Z DTSTAMP:20260423T022835Z UID:GSMMA/6 DESCRIPTION:Title: Va riational implicit-solvent predictions of the ligand-receptor (un)binding kinetics\nby Bo Li (University of California\, San Diego) as part of G lobal Seminar on Mathematical Modeling and Applications\n\n\nAbstract\nLig and-receptor binding and unbinding are fundamental molecular processes\, a nd are particularly essential to drug efficacy\, whereas water fluctuation s impact the corresponding thermodynamics and kinetics. We develop a varia tional implicit-solvent model (VISM) to calculate the potential of mean fo rce (PMF) as well as the solute-solvent interfacial structures of dry and wet states for a model ligand-pocket system. We also combine our VISM with the string method for transition paths to obtain the dry-wet transition r ates\, and conduct two-state Brownian dynamics simulations of the ligand s tochastic motion\, providing the mean first-passage times for the ligand-p ocket binding and unbinding. We find that the dewetting transition around the pocket is slowed down as the ligand approaches the pocket but is peake d suddenly once the ligand enters the pocket. In contrast to binding\, the ligand unbinding involves a much larger timescale due to a high energy ba rrier at the pocket entrance. The dry-wet fluctuation slows down the bindi ng but accelerates the unbinding process. Without any explicit description of individual water molecules\, our predictions are in a very good\, qual itative and semi-quantitative\, agreement with existing explicit-water mol ecular dynamics simulations\, providing a promising step in further effici ent studies of the ligand-receptor binding/unbinding kinetics. This is joi nt work with Shenggao Zhou\, R. Gregor Weiss\, Li-Tien Cheng\, Joachim Dzu biella\, and J. Andrew McCammon.\n\ntalk has ended\n LOCATION:https://researchseminars.org/talk/GSMMA/6/ END:VEVENT END:VCALENDAR