Dynamics and thermodynamics of beta-hairpin assembly: insights from various simulation techniques.

Small peptides that might have some features of globular proteins can provide important insights into the protein folding problem. Two simulation methods, Monte Carlo Dynamics (MCD), based on the Metropolis sampling scheme, and Entropy Sampling Monte Carlo (ESMC), were applied in a study of a high-resolution lattice model of the C-terminal fragment of the B1 domain of protein G. The results provide a detailed description of folding dynamics and thermodynamics and agree with recent experimental findings (. Nature. 390:196-197). In particular, it was found that the folding is cooperative and has features of an all-or-none transition. Hairpin assembly is usually initiated by turn formation; however, hydrophobic collapse, followed by the system rearrangement, was also observed. The denatured state exhibits a substantial amount of fluctuating helical conformations, despite the strong beta-type secondary structure propensities encoded in the sequence.