Correlation between knowledge-based and detailed atomic potentials: Application to the unfolding of the GCN4 leucine zipper

The relationship between the unfolding pseudo free energies of reduced and detailed atomic models of the GCN4 leucine zipper is examined. Starting fro m the native crystal structure, a large number of conformations ranging fro m folded to unfolded were generated by all-atom molecular dynamics unfoldin g simulations in an aqueous environment at elevated temperatures. For the d etailed atomic model, the pseudo free energies are obtained by combining th e CHARMM all-atom potential with a solvation component from the generalized Born, surface accessibility, GB/SA, model. Reduced model energies were eva luated using a knowledge-based potential. Both energies are highly correlat ed. In addition, both show a good correlation with the root mean square dev iation, RMSD, of the backbone from native. These results suggest that knowl edge-based potentials are capable of describing at least some of the proper ties of the folded as well as the unfolded states of proteins, even though they are derived from a database of native protein structures. Since only c onformations generated from an unfolding simulation are used, we cannot ass ess whether these potentials can discriminate the native conformation from the manifold of alternative, low-energy misfolded states. Nevertheless, the se results also have significant implications for the development of a meth odology for multiscale modeling of proteins that combines reduced and detai led atomic models. Proteins 1999;35:447-452, (C) 1999 Wiley-Liss, Inc.