FOLDING PROTEINS WITH A SIMPLE ENERGY FUNCTION AND EXTENSIVE CONFORMATIONAL SEARCHING

We describe a computer algorithm for predicting the three-dimensional structures of proteins using only their amino acid sequences. The meth od differs from others in two ways: (I)it uses very few energy paramet ers, representing hydrophobic and polar interactions, and (2) it uses a new ''constraint-based exhaustive'' searching method, which appears to be among the fastest and most complete search methods yet available for realistic protein models. It finds a relatively small number of l ow-energy conformations, among which are native-like conformations, fo r crambin (1CRN), avian pancreatic polypeptide (1PPT), melittin (2MLT) , and apamin. Thus, the lowest-energy states of very simple energy fun ctions may predict the native structures of globular proteins.