Sampling errors in free energy simulations of small molecules in lipid bilayers

Chris Neale; Régis Pomès

doi:10.1016/j.bbamem.2016.03.006

Sampling errors in free energy simulations of small molecules in lipid bilayers

Biochim Biophys Acta. 2016 Oct;1858(10):2539-2548. doi: 10.1016/j.bbamem.2016.03.006. Epub 2016 Mar 4.

Authors

Chris Neale¹, Régis Pomès²

Affiliations

¹ Department of Physics, Applied Physics and Astronomy, Rensselaer Polytechnic Institute, 110 8th St, Troy, New York 12180-3590, USA.
² 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.

PMID: 26952019
DOI: 10.1016/j.bbamem.2016.03.006

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.

Keywords: Free energy; Hidden barrier; Orthogonal barrier; Potential of mean force; Review; Simulation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Lipid Bilayers / chemistry*
Molecular Conformation
Molecular Dynamics Simulation*
Thermodynamics*

Substances

Lipid Bilayers