title: Beta-hairpin restraint potentials for calculations of potentials of mean force as a function of beta-hairpin tilt, rotation, and distance.
abstract: We have developed a set of restraint potentials for beta-hairpin tilt relative to the membrane normal, beta-hairpin rotation around the beta-hairpin axis, and hairpin-hairpin distance. Such restraint potentials enable us to characterize the molecular basis of specific beta-hairpin tilt and rotation in membranes and hairpin-hairpin interactions at the atomic level by sampling their conformational space along these degrees of freedom, i.e., reaction coordinates, during molecular dynamics simulations. We illustrate the efficacy of the beta-hairpin restraint potentials by calculating the potentials of mean force (PMFs) as a function of tilt and rotation angles of protegrin-1 (PG-1), a beta-hairpin antimicrobial peptide, in an implicit membrane model. The peptide association in the membrane is also examined by calculating the PMFs as a function of distance between two PG-1 peptides in various dimer interfaces. These novel restraint potentials are found to perform well in each of these cases and are expected to be a useful means to study the microscopic driving forces of insertion, tilting, and rotation of beta-hairpin peptides in membranes as well as their association in aqueous solvent or membrane environments particularly when combined with explicit solvent models.
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.forename: Sihyun
authors.initials: S
authors.lastname: Ham
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012399:Rotation
chemical_list: D023181:Antimicrobial Cationic Peptides; C094880:protegrin-1