Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model

We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein - Trp- cage - from a fully extended conformation. We demonstrate the ability of the Trp- cage model to consistently reach conformations within 2-Angstrom backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp- cage conformations in simulations can be <1 angstrom. Our findings suggest that, at least in the case of Trp- cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp- cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.