Native topology or specific interactions: What is more important for protein folding?
Title | Native topology or specific interactions: What is more important for protein folding? |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Ferrara P., Caflisch A. |
Journal | Journal of Molecular Biology |
Volume | 306 |
Issue | 4 |
Pagination | 837-850 |
Date Published | 2001 Mar 2 |
Type of Article | Research Article |
Keywords | Computer Simulation, Hydrogen Bonding, Kinetics, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Peptides, Protein Denaturation, Protein Folding, Protein Structure, Secondary, Thermodynamics |
Abstract | Fifty-five molecular dynamics runs of two three-stranded antiparallel β-sheet peptides were performed to investigate the relative importance of amino acid sequence and native topology. The two peptides consist of 20 residues each and have a sequence identity of 15 %. One peptide has Gly-Ser (GS) at both turns, while the other has d-Pro-Gly ((D)PG). The simulations successfully reproduce the NMR solution conformations, irrespective of the starting structure. The large number of folding events sampled along the trajectories at 360 K (total simulation time of about 5 micros) yield a projection of the free-energy landscape onto two significant progress variables. The two peptides have compact denatured states, similar free-energy surfaces, and folding pathways that involve the formation of a β-hairpin followed by consolidation of the unstructured strand. For the GS peptide, there are 33 folding events that start by the formation of the 2-3 β-hairpin and 17 with first the 1-2 β-hairpin. For the (D)PG peptide, the statistical predominance is opposite, 16 and 47 folding events start from the 2-3 β-hairpin and the 1-2 β-hairpin, respectively. These simulation results indicate that the overall shape of the free-energy surface is defined primarily by the native-state topology, in agreement with an ever-increasing amount of experimental and theoretical evidence, while the amino acid sequence determines the statistically predominant order of the events. |
DOI | 10.1006/jmbi.2000.4400 |
pubindex | 0030 |
Alternate Journal | J. Mol. Biol. |
PubMed ID | 11243792 |