title: Sampling errors in free energy simulations of small molecules in lipid bilayers.
abstract: Free energy simulations are a powerful tool for evaluating the interactions of molecular solutes with lipid bilayers as mimetics of cellular membranes. However, these simulations are frequently hindered by systematic sampling errors. This review highlights recent progress in computing free energy profiles for inserting molecular solutes into lipid bilayers. Particular emphasis is placed on a systematic analysis of the free energy profiles, identifying the sources of sampling errors that reduce computational efficiency, and highlighting methodological advances that may alleviate sampling deficiencies. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
authors.affiliation: Department of Physics, Applied Physics and Astronomy, Rensselaer Polytechnic Institute, 110 8th St, Troy, New York 12180-3590, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Neale
authors.affiliation: Molecular Structure and Function, The Hospital for Sick Children, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada; Department of Biochemistry, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada. Electronic address: pomes@sickkids.com.
authors.forename: Régis
authors.initials: R
authors.lastname: Pomès
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers
keywords: Free energy; Hidden barrier; Orthogonal barrier; Potential of mean force; Review; Simulation