Exploring the free-energy landscapes of biological systems with steered molecular dynamics

摘要: We perform steered molecular dynamics (SMD) simulations and use the Brownian fluctuation-dissipation-theorem (BD-FDT) to accurately compute free-energy profiles for several biophysical processes of fundamental importance: hydration methane cations, binding benzene T4-lysozyme L99A mutant, permeation water through aquaglyceroporin. For each system, center-of-mass small molecule (methane, ion, benzene, water, respectively) is (pulled) at a given speed over period time, during which system transitions from one macroscopic state/conformation (State A) another B). The mechanical work pulling measured process, sampling forward path. Then reverse conducted sample path B back A. Sampling number paths, we are able all afore-listed systems that represent various important aspects biological physics. numerical results in excellent agreement with experimental data and/or other computational studies available literature.