LEARNING ABOUT PROTEIN-FOLDING VIA POTENTIAL FUNCTIONS

Over the last few years we have developed an empirical potential funct ion that solves the protein structure recognition problem: given the s equence for an n-residue globular protein and a collection of plausibl e protein conformations, including the native conformation for that se quence, identify the correct, native conformation. Having determined t his potential on the basis of only some 6500 native/nonnative pairs of structures for 58 proteins, we find it recognizes the native conforma tion for essentially all compact, soluble, globular proteins having kn own native conformations in comparisons with 10(4) to 10(6) reasonable alternative conformations apiece. In this sense, the potential encode s nearly all the essential features of globular protein conformational preference. In addition it ''knows'' about many additional factors in protein folding, such as the stabilization of multimeric proteins, qu aternary structure, the role of disulfide bridges and ligands, proprot eins vs. processed proteins, and minimal strand lengths in globular pr oteins. Comparisons are made with other sorts of protein folding probl ems, and applications in protein conformational determination and pred iction are discussed. (C) 1994 Wiley-Liss, Inc.