title: Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly.
abstract: The method of window exchange umbrella sampling molecular dynamics (WEUSMD) with a pre-optimized parameter set was recently used to obtain the most probable conformations and the energetics of transmembrane (TM) helix assembly of a generic TM sequence. When applied to glycophorin A TM domain (GpA-TM) using the restraint potentials along the helix-helix distance, however, tight interfacial packing of GpA-TM resulted in insufficient conformational sampling at short helix-helix separation. This sampling issue is addressed by extending the WEUSMD into two dimensions with the restraint potentials along the helix-helix distance and crossing angle. The two-dimensional WEUSMD results demonstrate that the incomplete sampling in the one-dimensional WEUSMD arises from high barriers along the crossing angle between the GpA-TM helices. Together with the faster convergence in both the assembled conformations and the potential of mean force, the 2D-WEUSMD can be a general and efficient approach in computational studies of TM helix assembly.
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA.
authors.forename: Soohyung
authors.initials: S
authors.lastname: Park
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
keywords: First Passage Time Optimization; Glycophorin A; Potential of Mean Force; Replica Exchange Methods