Abstract: The ability to discriminate native structures from computer-generated misfolded ones is key to predicting the three-dimensional structure of a protein from its amino acid sequence. Here we describe an assessment of semiempirical methods for discriminating native protein structures from decoy models. The discrimination of decoys entails an analysis of a large number of protein structures and provides a large-scale validation of quantum mechanical methods and their ability to accurately model proteins. We combine our analysis of semiempirical methods with a comparison of an AMBER force field to discriminate decoys in conjunction with a continuum solvent model. Protein decoys provide a rigorous and reliable benchmark for the evaluation of scoring functions, not only in their ability to accurately identify native structures but also to be computationally tractable to sample a large set of non-native models.

Authors: Andrew M. Wollacott and Kenneth M. Merz, Jr.

Reference: Journal of Chemical Theory and Computation. 2007, ASAP Article. (see link for full paper).