Simulation of protein folding by reaction path annealing

摘要: We present a systematic application of reaction path sampling to computer simulations the folding peptides and small proteins at atomic resolution in presence solvent. use simulated annealing protocol generate an ensemble room temperature trajectories fixed length, which connect predetermined initial final states. The are distributed according discretized version Onsager–Machlup action functional. show that, despite enormous practical restrictions placed on number time slices can be explored, some basic kinetic features found experimentally for exhibited nature paths sampled. test method three systems: A 12 residue α-helical peptide, 16 β-hairpin 36 avian Pancreatic Polypeptide (aPP). All systems represented resolution, include explicit water molecules. For α-helix, we find that (i,i+3) hydrogen bonds play significant role pathway, with specific appearing, then transforming corresponding (i,i+4) bond some, but not all native bonds. aPP, hydrophobic interactions dominant role, nonbonded consistently appearing before This is true both level tertiary structure, individual tend form only after stabilizing have already formed between residues involved.