In quest of an empirical potential for protein structure prediction.

Key to successful protein structure prediction is a potential that recognizes the native state from misfolded structures. Recent advances in empirical potentials based on known protein structures include improved reference states for assessing random interactions, sidechain-orientation-dependent pair potentials, potentials for describing secondary or supersecondary structural preferences and, most importantly, optimization protocols that sculpt the energy landscape to enhance the correlation between native-like features and the energy. Improved clustering algorithms that select native-like structures on the basis of cluster density also resulted in greater prediction accuracy. For template-based modeling, these advances allowed improvement in predicted structures relative to their initial template alignments over a wide range of target-template homology. This represents significant progress and suggests applications to proteome-scale structure prediction.