Improving the performance of Rosetta using multiple sequence alignment information and global measures of hydrophobic core formation

This study explores the use of multiple sequence alignment (MSA) informatio n and global measures of hydrophobic core formation for improving the Roset ta ab initio protein structure prediction method. The most effective use of the MSA information is achieved by carrying out independent folding simula tions for a subset of the homologous sequences in the MSA and then identify ing the free energy minima common to all folded sequences via simultaneous clustering of the independent folding runs, Global measures of hydrophobic core formation, using ellipsoidal rather than spherical representations of the hydrophobic core, are found to be useful in removing non-native conform ations before cluster analysis. Through this combination of MSA information and global measures of protein core formation, we significantly increase t he performance of Rosetta on a challenging test set. Proteins 2001;43:1-11. (C) 2001 Wiley-Liss, Inc.