Prospects for ab initio protein structural genomics

We present the results of a large-scale testing of the ROSETTA method for a b initio protein structure prediction. Models were generated for two indepe ndently generated lists of small proteins (up to 150 amino acid residues), and the results were evaluated using traditional rmsd based measures and a novel measure based on the structure-based comparison of the models to the structures in the PDB using DALI. For 111 of 136 all alpha and alpha/beta p roteins 50 to 150 residues in length, the method produced at least one mode l within 7 Angstrom rmsd of the native structure in 1000 attempts. For 60 o f these proteins, the closest structure match in the PDB to at least one of the ten most frequently generated conformations was found to be structural ly related (four standard deviations above background) to the native protei n. These results suggest that ab initio structure prediction approaches may soon be useful for generating low resolution models and identifying distan tly related proteins with similar structures and perhaps functions for thes e classes of proteins on the genome scale. (C) 2001 Academic Press.