%0 Journal Article %T A Model for Protein Sequence Evolution Based on Selective Pressure for Protein Stability: Application to Hemoglobins %A Lorraine Marsh %J Evolutionary Bioinformatics %D 2009 %I %X Negative selection against protein instability is a central influence on evolution of proteins. Protein stability is maintained over evolution despite changes in underlying sequences. An empirical all-site stability-based model of evolution was developed to focus on the selection of residues arising from their contributions to protein stability. In this model, site rates could vary. A structure-based method was used to predict stationary frequencies of hemoglobin residues based on their propensity to promote protein stability at a site. Sites with destabilizing residues were shown to change more rapidly in hemoglobins than sites with stabilizing residues. For diverse proteins the results were consistent with stability-based selection. Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods. These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution. %U http://la-press.com/a-model-for-protein-sequence-evolution-based-on-selective-pressure-for-a1608