Folding Very Short Peptides Using Molecular Dynamics 英文参考文献.docVIP

FoldingVeryShortPeptidesUsing MolecularDynamics Bosco K. Ho*,Ken A.Dill DepartmentofPharmaceuticalChemistry,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica 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- accessibleelectrostaticapproximationtowater)implicitsolvent.Wefoundthat85ofthepeptideshavenopreferred 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 backbonedescription.Inparticular,allsevenofthebhairpinsinthenativestructurescontainafragmentintheturn 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 assemblyofpeptidefragments. Citation:HoBK,DillKA(2006)Foldingveryshortpeptidesusingmoleculardynamics.PLoSComputBiol2(4):e27.DOI:10.1371/journal.pcbi.0020027 Here, we study 133 peptide 8-mer fragments from six different proteins of different folds, using replica-exchange Introduction Peptidefragmentsofproteinsoftenhaveintrinsicpropen- sities for the formation of their native conformations. For example, NMR experiments [1] show that long peptide fragments have native-like conformations [2–7]. Some short peptidesinsolutionhavealsobeenshowntoadopttheirnative secondarystructures:ahelices[8,9]andbhairpins[10–14]. As a consequence, peptide conformational propensities that are taken from the protein databank (PDB) [1–17] are now widely used in protein-structure prediction algorithms. Apopularsetofpeptidefragmentconf