TERTIARY STRUCTURE PREDICTION USING MEAN-FORCE POTENTIALS AND INTERNAL ENERGY FUNCTIONS - SUCCESSFUL PREDICTION FOR COILED-COIL

We report a preliminary study of the use of mean-force potentials (MFP s) for predicting protein tertiary structure. For three leucine zipper sequences, we have calculated ensembles of structures spanning all po ssible backbone conformations consistent with the canonical coiled coi l geometry. MFPs were measured with the program PROSA. The MFP alone w as poor at discriminating the native structure from very divergent str uctures, and the global minimum of the MFP sometimes occurred far from the native structure. We found that adding an internal energy functio n (a subset of the CHARMM potential that describes only interactions b etween backbone atoms), the resultant total energy (CHARMM+PROSA) perf ormed much better; in each case, there was a clear positive correlatio n between total energy and root-mean square deviation (RMSD) from the experimental structure, and the lowest-energy structures were about 1 Angstrom RMSD from the experimental structures. Thus, we conclude that the combined potential is a powerful method for predicting leucine ti ppers and is very promising for general 3D structure prediction.