Average assignment method for predicting the stability of protein mutants

Prediction of protein stability upon ann. no acid substitutions is an important problem in molecular biology and it will be helpful for designing stable mutants. In this work we have analyzed the stability of protein mutants using three different data sets of 1791, 1396, and 2204 mutants, respectively, for thermal stability (Delta T-m), free energy change due to thermal (Delta Delta G), and denaturant denaturations (Delta Delta G(H2O)), obtained from the ProTherm database. We have classified the mutants into 380 possible substitutions and assigned the stability of each mutant using the information obtained with similar type of mutations. We observed that this assignment could distinguish the stabilizing and destabilizing Mutants to an accuracy of 70-80% at different measures of stability. Further, we have classified the mutants based on secondary structure and solvent accessibility (ASA) and observed that the classification significantly improved the accuracy of prediction. The classification of mutants based on helix. strand, and coil distinguished the stabilizing destabilizing mutants at an average accuracy of 82% and the correlation is 0.56; information about the location of residues at the interior, partially buried, and surface regions of a protein correctly identified the stabilizing/destabilizing residues at an average accuracy of 81% and the correlation is 0.59. The nine subclassifications based on three secondary structures and solvent accessibilities improved the accuracy of assigning stabilizing/destabilizing mutants to an accuracy of 84-89% for the three data sets. Further, the present method is able to predict the free energy change (Delta Delta G) upon mutations within a deviation of 0.64 kcal/mol. We suggest that this method could be used for predicting the stability of protein mutants. (c) 2006 Wiley Periodicals, Inc.