A novel parameterization scheme for energy equations and its use to calculate the structure of protein molecules.

A novel scheme for the parameterization of a type of "potential energy" function for protein molecules is introduced. The function is parameterized based on the known conformations of previously determined protein structures and their sequence similarity to a molecule whose conformation is to be calculated. Once parameterized, minima of the potential energy function can be located using a version of simulated annealing which has been previously shown to locate global and near-global minima with the given functional form. As a test problem, the potential was parameterized based on the known structures of the rubredoxins from Desulfovibrio vulgaris, Desulfovibrio desulfuricans, and Clostridium pasteurianum, which vary from 45 to 54 amino acids in length, and the sequence alignments of these molecules with the rubredoxin sequence from Desulfovibrio gigas. Since the Desulfovibrio gigas rubredeoxin conformation has also been determined, it is possible to check the accuracy of the results. Ten simulated-annealing runs from random starting conformations were performed. Seven of the 10 resultant conformations have an all-C alpha rms deviation from the crystallographically determined conformation of less than 1.7 A. For five of the structures, the rms deviation is less than 0.8 A. Four of the structures have conformations which are virtually identical to each other except for the position of the carboxy-terminal residue. This is also the conformation which is achieved if the determined crystal structure is minimized with the same potential. The all-C alpha rms difference between the crystal and minimized crystal structures is 0.6 A.(ABSTRACT TRUNCATED AT 250 WORDS)