title: Decrypting protein insertion through the translocon with free-energy calculations.
abstract: Protein insertion into a membrane is a complex process involving numerous players. The most prominent of these players is the Sec translocon complex, a conserved protein-conducting channel present in the cytoplasmic membrane of bacteria and the membrane of the endoplasmic reticulum in eukaryotes. The last decade has seen tremendous leaps forward in our understanding of how insertion is managed by the translocon and its partners, coming from atomic-detailed structures, innovative experiments, and well-designed simulations. In this review, we discuss how experiments and simulations, hand-in-hand, teased out the secrets of the translocon-facilitated membrane insertion process. In particular, we focus on the role of free-energy calculations in elucidating membrane insertion. Amazingly, despite all its apparent complexity, protein insertion into membranes is primarily driven by simple thermodynamic and kinetic principles. This article is part of a Special Issue entitled: Membrane proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: gumbart@physics.gatech.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Gumbart
authors.affiliation: Laboratoire International Associé Centre National de la Recherche Scientifique and University of Illinois at Urbana-Champaign, UMR n° 7565, Université de Lorraine, B.P. 70239, 54506 Vandœuvre-lès-Nancy, France; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: chipot@ks.uiuc.edu.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chipot
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D004735:Energy Transfer; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins
keywords: Free-energy calculations; Importance-sampling algorithms; Protein insertion; Sec translocon complex