Folding very short peptides using molecular dynamics.
Peptides often have conformational preferences. We simulated 133 peptide 8-mer fragments from six different proteins, sampled by replica-exchange molecular dynamics using Amber7 with a GB/SA (generalized-Born/solvent-accessible electrostatic approximation to water) implicit solvent. We found that 85 of the peptides have no preferred structure, while 48 of them converge to a preferred structure. In 85% of the converged cases (41 peptides), the structures found by the simulations bear some resemblance to their native structures, based on a coarse-grained backbone description. In particular, all seven of the beta hairpins in the native structures contain a fragment in the turn that is highly structured. In the eight cases where the bioinformatics-based I-sites library picks out native-like structures, the present simulations are largely in agreement. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.
Ho
Bosco K
BK
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA. bosco@maxwell.ucsf.edu
Dill
Ken A
KA
D055592:Biophysical Phenomena; D001703:Biophysics; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D019277:Entropy; D007700:Kinetics; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D040901:Proteomics / Q000379:methods; D012997:Solvents / Q000737:chemistry
D010455:Peptides; D012997:Solvents