title: Free energy surfaces of beta-hairpin and alpha-helical peptides generated by replica exchange molecular dynamics with the AGBNP implicit solvent model.
abstract: We have studied the potential of mean force of two peptides, one known to adopt a beta-hairpin and the other an alpha-helical conformation in solution. These peptides are, respectively, residues 41-56 of the C-terminus (GEWTYDDATKTFTVTE) of the B1 domain of protein G and the 13 residue C-peptide (KETAAAKFERQHM) of ribonuclease A. Extensive canonical ensemble sampling has been performed using a parallel replica exchange method. The effective potential employed in this work consists of the OPLS all-atom force field (OPLS-AA) and an analytical generalized Born (AGB) implicit solvent model including a novel nonpolar solvation free energy estimator (NP). An additional dielectric screening parameter has been incorporated into the AGBNP model. In the case of the beta-hairpin, the nonpolar solvation free energy estimator provides the necessary effective interactions for the collapse of the hydrophobic core (W43, Y45, F52, and V54), which the more commonly used surface-area-dependent nonpolar model does not provide. For both the beta-hairpin and the alpha-helix, increased dielectric screening reduces the stability of incorrectly formed salt bridges, which tend to disrupt the formation of the hairpin and helix, respectively. The fraction of beta-hairpin and alpha-helix content we obtained using the AGBNP model agrees well with experimental results. The thermodynamic stability of the beta-hairpin from protein G and the alpha-helical C-peptide from ribonuclease A as modeled with the OPLS-AA/AGBNP effective potential reflects the balance between the nonpolar effective potential terms, which drive compaction, and the polar and hydrogen bonding terms, which promote secondary structure formation.
authors.affiliation: Department of Chemistry and Chemical Biology and BIOMAPS Institute for Quantitative Biology, Rutgers University, Wright-Rieman Laboratories, 610 Taylor Rd, Piscataway, New Jersey 08854-8087, USA.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Felts
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Harano
authors.forename: Emilio
authors.initials: E
authors.lastname: Gallicchio
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Levy
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012996:Solutions; D012997:Solvents; D013696:Temperature; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; C029152:G-substrate; D009419:Nerve Tissue Proteins; D012996:Solutions; D012997:Solvents; D012259:Ribonuclease, Pancreatic