title: The influence of different treatments of electrostatic interactions on the thermodynamics of folding of peptides.
abstract: Replica exchange molecular dynamics simulations were performed to investigate the effects of different electrostatic treatments on the structure and thermodynamics of a small beta-hairpin forming peptide. Three different electrostatic schemes were considered: regular cutoffs, generalized reaction field (GRF), and particle mesh Ewald (PME), with the peptide modeled using OPLS/AA all-atom force field with explicit TIP3P water. Both the GRF and PME methods yielded results consistent with experiment, with free energy surfaces displaying a single minimum corresponding to the native beta-hairpin structure. In contrast, use of straight cutoffs led to the population of an additional local minimum corresponding to nonhairpin conformations that compete with the formation of the native beta-hairpin at low temperatures. This extra minimum would not be apparent in conventional constant-temperature molecular dynamics simulations run for a few nanoseconds. This result points to the critical need of careful sampling of conformational space to assess the quality of different numerical treatments of long-range forces. While differences emerged in the nature of the unfolded states populated using PME and GRF approaches, simulations on the beta-hairpin forming peptide and on two additional control peptides indicate that the GRF treatment of electrostatics offers a satisfactory compromise between accuracy and computational speed for the identification of low-energy conformations. A GRF-based approach emerges as a viable means for treating larger biological systems that would be prohibitively costly to simulate using PME methods.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
authors.forename: Andrij
authors.initials: A
authors.lastname: Baumketner
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D010455:Peptides