title: Exploring substrate diffusion in channels using biased molecular dynamics simulations.
abstract: Substrate transport and diffusion through membrane-bound channels are processes that can span a range of time scales, with only the fastest ones being amenable to most atomic-scale equilibrium molecular dynamics (MD) simulations. However, the application of forces within a simulation can greatly accelerate diffusion processes, revealing important structural and energetic features of the channel. Here, we demonstrate the use of two methods for applying biases to a substrate in a simulation, using the ammonia/ammonium transporter AmtB as an example. The first method, steered MD, applies a constant force or velocity constraint to the substrate, permitting the exploration of potential substrate pathways and the barriers encountered, although typically far outside of equilibrium. On the other hand, the second method, adaptive biasing forces, is quasi-equilibrium, permitting the derivation of a potential of mean force, which characterizes the free energy of the substrate during transport.
authors.affiliation: Biosciences Division, Argonne National Laboratory, Argonne, IL, USA. gumbart@mcs.anl.gov
authors.forename: James
authors.initials: J
authors.lastname: Gumbart
mesh_terms: D027682:Cation Transport Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004058:Diffusion; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D013379:Substrate Specificity
chemical_list: C111096:AmtB protein, E coli; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels