Ab initio folding of proteins using restraints derived from evolutionary information

We present our predictions in the ab initio structure prediction category o f CASP3, Eleven targets were folded, using a method based on a Monte Carlo search driven by secondary and tertiary restraints derived from multiple se quence alignments. Our results can be qualitatively summarized as follows: The global fold can be considered "correct" for targets 65 and 74, "almost correct" for targets 64, 75, and 77, "half-correct" for target 79, and "wro ng" for targets 52, 56, 59, and 63, Target 72 has not yet been solved exper imentally. On average, for small helical and alpha/beta proteins (on the or der of 110 residues or smaller), the method predicted low resolution struct ures with a reasonably good prediction of the global topology. Most encoura ging is that in some situations, such as with target 75 and, particularly t arget 77, the method can predict a substantial portion of a rare or even a novel fold. However, the current method still fails on some beta proteins, proteins over the 110-residue threshold, and sequences in which only a poor multiple sequence alignment can be built. On the other hand, for small pro teins, the method gives results of quality at least similar to that of thre ading, with the advantage of not being restricted to known folds in the pro tein database, Overall, these results indicate that some progress has been made on the ab initio protein folding problem, Detailed information about o ur results can be obtained by connecting to http://www.bioinformatics.danfo rthcenter.org/CASP3. (C) 1999 Wiley-Liss, Inc.