title: Prediction of folding equilibria of differently substituted peptides using one-step perturbation.
abstract: Computer simulation using long molecular dynamics (MD) can be used to simulate the folding equilibria of peptides and small proteins. However, a systematic investigation of the influence of the side-chain composition and position at the backbone on the folding equilibrium is computationally as well as experimentally too expensive because of the exponentially growing number of possible side-chain compositions and combinations along the peptide chain. Here, we show that application of the one-step perturbation technique may solve this problem, at least computationally; that is, one can predict many folding equilibria of a polypeptide with different side-chain substitutions from just one single MD simulation using an unphysical reference state. The methodology reduces the number of required separate simulations by an order of magnitude.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, 8093 Zrich, Switzerland.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.forename: Jörgen
authors.initials: J
authors.lastname: Kornfeld
authors.forename: Markus
authors.initials: M
authors.lastname: Mächler
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D009842:Oligopeptides