title: The cellular membrane as a mediator for small molecule interaction with membrane proteins.
abstract: The cellular membrane constitutes the first element that encounters a wide variety of molecular species to which a cell might be exposed. Hosting a large number of structurally and functionally diverse proteins associated with this key metabolic compartment, the membrane not only directly controls the traffic of various molecules in and out of the cell, it also participates in such diverse and important processes as signal transduction and chemical processing of incoming molecular species. In this article, we present a number of cases where details of interaction of small molecular species such as drugs with the membrane, which are often experimentally inaccessible, have been studied using advanced molecular simulation techniques. We have selected systems in which partitioning of the small molecule with the membrane constitutes a key step for its final biological function, often binding to and interacting with a protein associated with the membrane. These examples demonstrate that membrane partitioning is not only important for the overall distribution of drugs and other small molecules into different compartments of the body, it may also play a key role in determining the efficiency and the mode of interaction of the drug with its target protein. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States. Electronic address: cmayne2@illinois.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mayne
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, United States; College of Medicine, University of Illinois at Urbana-Champaign, United States. Electronic address: marcar2@illinois.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Arcario
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, United States. Electronic address: mahinth1@illinois.edu.
authors.forename: Paween
authors.initials: P
authors.lastname: Mahinthichaichan
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, United States. Electronic address: baylonc2@illinois.edu.
authors.forename: Javier L
authors.initials: JL
authors.lastname: Baylon
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, United States. Electronic address: vermaas2@illinois.edu.
authors.forename: Josh V
authors.initials: JV
authors.lastname: Vermaas
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States. Electronic address: lnavid@illinois.edu.
authors.forename: Latifeh
authors.initials: L
authors.lastname: Navidpour
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States. Electronic address: pwen2@illinois.edu.
authors.forename: Po-Chao
authors.initials: PC
authors.lastname: Wen
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, United States. Electronic address: sundar81@illinois.edu.
authors.forename: Sundarapandian
authors.initials: S
authors.lastname: Thangapandian
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, United States; Department of Biochemistry, University of Illinois at Urbana-Champaign, United States; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, United States; College of Medicine, University of Illinois at Urbana-Champaign, United States. Electronic address: emad@life.illinois.edu.
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
mesh_terms: D000777:Anesthetics / Q000493:pharmacokinetics / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000502:physiology; D003576:Electron Transport Complex IV / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000378:metabolism; D013256:Steroids / Q000493:pharmacokinetics
chemical_list: D000777:Anesthetics; D008565:Membrane Proteins; D013256:Steroids; D051544:Cytochrome P-450 CYP3A; D003576:Electron Transport Complex IV; D010100:Oxygen
keywords: Membrane; Membrane proteins; Molecular dynamics; Small molecules