MOLECULAR SIMULATIONS OF PEPTIDE AND PROTEIN UNFOLDING - IN QUEST OF A MOLTEN GLOBULE

Calculations based on molecular dynamics simulations have been used to explore peptide and protein unfolding in aqueous solution. Insights from simulation studies into the timescales and mechanism of helix and turn formation and dissolution suggest that helices unfold through turn-like intermediates on timescales of nanoseconds. Recent applications of simulation methods to the study of compact non-native states of proteins illustrate the richness of properties which may be extracted from such detailed calculations. Such properties include the characterization of putative molten globules for lysozyme and pancreatic trypsin inhibitor using a variety of denaturing conditions. Comparisons with experimental findings, where available, are in general agreement with most of the simulation studies, and point to the future role simulations can play in unraveling detailed aspects of protein folding.