Understanding ensemble protein folding at atomic detail

Abstract

Although far from routine, simulating the folding of specific short protein chains on thecomputer, at a detailed atomic level, is starting to become a reality. This remarkableprogress, which has been made over the last decade or so, allows a fundamental aspect ofthe protein folding process to be addressed, namely its statistical nature. In order to makequantitative comparisons with experimental kinetic data a complete ensemble view offolding must be achieved, with key observables averaged over the large number ofmicroscopically different folding trajectories available to a protein chain. Here we reviewrecent advances in atomic-level protein folding simulations and the new insight provided bythem into the protein folding process. An important element in understanding ensemblefolding kinetics are methods for analyzing many separate folding trajectories, andwe discuss techniques developed to condense the large amount of informationcontained in an ensemble of trajectories into a manageable picture of the foldingprocess.