Matching simulation and experiment: A new simplified model for simulating protein folding

Simulations of simplified protein folding models have provided much insight into solving the protein folding problem, We propose here a new off-lattic e bead model, capable of simulating several different fold classes of small proteins. We present the sequence for an alpha/beta protein resembling the IgG-binding proteins L and G. The thermodynamics of the folding process fo r this model are characterized using the multiple multihistogram method com bined with constant-temperature Langevin simulations, The folding is shown to be highly cooperative, with chain collapse nearly accompanying folding, Two parallel folding pathways are shown to exist on the folding free energy landscape, One pathway contains an intermediate-similar to experiments on protein G, and one pathway contains no intermediates-similar to experiments on protein L, The folding kinetics are characterized by tabulating mean-fi rst passage times, and we show that the onset of glasslike kinetics occurs at much lower temperatures than the folding temperature, This model is expe cted to be useful in many future contexts: investigating questions of the r ole of local versus nonlocal interactions in various fold classes, addressi ng the effect of sequence mutations affecting secondary structure propensit ies, and providing a computationally feasible model for studying the role o f solvation forces in protein folding.