title: Understanding folding and design: replica-exchange simulations of "Trp-cage" miniproteins.
abstract: Replica-exchange molecular dynamics simulations in implicit solvent have been carried out to study the folding thermodynamics of a designed 20-residue peptide, or "miniprotein." The simulations in this study used the amber (parm94) force field along with the generalized Born/solvent-accessible surface area implicit solvent model, and they spanned a range of temperatures from 273 to 630 K. Starting from a completely extended initial conformation, simulations of one peptide sequence sample conformations that are <1.0 A Calpha rms positional deviation from structures in the corresponding NMR ensemble. These folded states are thermodynamically stable with a simulated melting temperature of approximately 400 K, and they satisfy the majority of experimentally observed NMR restraints. Simulations of a related mutant peptide show a degenerate ensemble of states at low temperature, in agreement with experimental results.
authors.affiliation: IBM Research, Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA. pitera@us.ibm.com
authors.forename: Jed W
authors.initials: JW
authors.lastname: Pitera
authors.forename: William
authors.initials: W
authors.lastname: Swope
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D013696:Temperature; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D010455:Peptides; D014364:Tryptophan