Ab initio protein structure prediction using a combined hierarchical approach

As part of the third Critical Assessment of Structure Prediction meeting (C ASP3), we predict the three-dimensional structures for 13 proteins using a hierarchical approach. First, all possible compact conformations of a prote in sequence are enumerated using a highly simplified tetrahedral lattice mo del. We select a large subset of these conformations using a lattice-based scoring function and build detailed all-atom models incorporating predicted secondary structure. A combined all-atom knowledge-based scoring function is then used to select three smaller subsets from these all-atom models. Fi nally, a consensus-based distance geometry procedure is used to generate th e best conformations from each of the all-atom subsets. With this method, w e are able to predict the global topology/shape for all or a large part of the sequence for six out of the thirteen proteins. For two other proteins, the topology/shape for shorter fragments are predicted. This represents a m arked improvement in ab initio prediction since GASP was first instigated i n 1994, (C) 1999 Wiley-Liss, Inc.