Understanding Folding and Design: Replica-Exchange Simulations of "Trp-Cage" Miniproteins

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 13; pp. 7587 - 7592
• Main Authors: Pitera, Jed W., Swope, William
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24.06.2003; National Acad Sciences
• Subjects: Biological Sciences; Biophysical Phenomena; Biophysics; Computer Simulation; Force field; Hot Temperature; Hydrogen bonds; Kinetics; Low temperature; Magnetic Resonance Spectroscopy; Melting; Modeling; Models, Molecular; Mutation; NMR; Nuclear magnetic resonance; Peptides; Peptides - chemistry; Protein Conformation; Protein Denaturation; Protein Folding; Proteins; Simulations; Solvents; Temperature; Thermodynamics; Tryptophan - chemistry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1330954100

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$<\!1.0\>\AA\>C^\alpha$rms positional deviation from structures in the corresponding NMR ensemble. These folded states are thermodynamically stable with a simulated melting temperature of$\approx\!400\>K$, 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.