title: Exploring the free-energy landscapes of biological systems with steered molecular dynamics.
abstract: We perform steered molecular dynamics (SMD) simulations and use the Brownian dynamics fluctuation-dissipation-theorem (BD-FDT) to accurately compute the free-energy profiles for several biophysical processes of fundamental importance: hydration of methane and cations, binding of benzene to T4-lysozyme L99A mutant, and permeation of water through aquaglyceroporin. For each system, the center-of-mass of the small molecule (methane, ion, benzene, and water, respectively) is steered (pulled) at a given speed over a period of time, during which the system transitions from one macroscopic state/conformation (State A) to another one (State B). The mechanical work of pulling the system is measured during the process, sampling a forward pulling path. Then the reverse pulling is conducted to sample a reverse path from B back to A. Sampling a small number of forward and reverse paths, we are able to accurately compute the free-energy profiles for all the afore-listed systems that represent various important aspects of biological physics. The numerical results are in excellent agreement with the experimental data and/or other computational studies available in the literature.
authors.affiliation: Department of Physics, University of Texas at San Antonio, San Antonio, Texas 78249, USA. Liao.Chen@utsa.edu
authors.forename: L Y
authors.initials: LY
authors.lastname: Chen
mesh_terms: D008024:Ligands; D008697:Methane / Q000737:chemistry; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D008024:Ligands; D011506:Proteins; D014867:Water; D008697:Methane