title: Folding and insertion thermodynamics of the transmembrane WALP peptide.
abstract: The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum-in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Tristan
authors.initials: T
authors.lastname: Bereau
authors.affiliation: Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: W F Drew
authors.initials: WF
authors.lastname: Bennett
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Pfaendtner
authors.affiliation: Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Deserno
authors.affiliation: Department of Mathematics and Computer Science & Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, MetaForum, 5600 MB Eindhoven, The Netherlands.
authors.forename: Mikko
authors.initials: M
authors.lastname: Karttunen
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010455:Peptides