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

Small peptides that might have some features of globular proteins can provi de important insights into the protein folding problem. Two simulation meth ods, Monte Carte Dynamics (MCD), based on the Metropolis sampling scheme, a nd Entropy Sampling Monte Carte (ESMC), were applied in a study of a high-r esolution lattice model of the C-terminal fragment of the BI domain of prot ein G. The results provide a detailed description of folding dynamics and t hermodynamics and agree with recent experimental findings (Munoz et al., 19 97. Nature. 390:196-197). In particular, it was found that the folding is c ooperative and has features of an all-or-none transition. Hairpin assembly is usually initiated by turn formation; however, hydrophobic collapse, foll owed by the system rearrangement, was also observed. The denatured state ex hibits a substantial amount of fluctuating helical conformations, despite t he strong beta-type secondary structure propensities encoded in the sequenc e.