Efficient potential of mean force calculation from multiscale simulations: Solute insertion in a lipid membrane

The determination of potentials of mean force for solute insertion in a lipid membrane by means of allatom molecular dynamics simulations is often hampered by sampling issues. Recently, a multiscale method has been proposed to leverage the conformational ensemble of a lower-resolution model as starting point for higher resolution simulations. In this work, we analyze the efficiency of this method by comparing its predictions for propanol insertion into a lipid membrane against conventional atomistic umbrella sampling simulation results. The multiscale approach is confirmed to provide accurate results with a gain of one order of magnitude in computational time. We then investigate the role of the coarsegrained representation. We find that the accuracy of the results is tightly connected to the presence of a good configurational overlap between the coarse-grained and atomistic models-a general requirement when developing multiscale simulation methods. (C) 2017 Elsevier Inc. All rights reserved.