Park, SoohyungIm, Wonpil2017-05-172017-05-172013Park, S., & Im, W. (2013). Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly. Journal of Chemical Theory and Computation, 9(1), 13–17. http://doi.org/10.1021/ct3008556https://hdl.handle.net/1808/24233The 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.This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ct3008556.Glycophorin AReplica Exchange MethodsFirst Passage Time OptimizationPotential of Mean ForceArticle10.1021/ct3008556https://orcid.org/0000-0002-4883-3031PMC3593060openAccess