Prediction of protein thermostability with a direction- and distance-dependent knowledge-based potential.
The increasing use of enzymes in industrial processes and the importance of understanding protein folding and stability have led to several attempts to predict and quantify the effect of every possible amino acid exchange (mutation) on the thermostability of proteins. In this article we describe a knowledge-based discrimination function that acts as a fast and reliable guide in protein engineering and optimization. The function used consists of two parts, a pairwise energy function based on a distance- and direction-dependent atomic description of the amino acid environment, and a torsion angle energy function. In a first step a training set of 11 proteins including 646 mutant proteins with experimentally determined thermostability was used to optimize the knowledge-based energy functions. The resulting potential function was then tested using a test mutant database consisting of 918 various point mutations introduced in 27 proteins. The best correlation coefficient obtained for the experimental data and the predicted thermostability for the training set is r = 0.81 (561 data points). A total of 76% of the mutations could be predicted correctly as being either stabilizing or destabilizing. The results for the test set are r = 0.74 (747 data points) and 72%, respectively. The global correlation over the combined data (1308 mutants) obtained is 0.78.
Hoppe
Christian
C
Institut für Biochemie, Zülpicher Strasse 47, 50674 Köln, Germany.
Schomburg
Dietmar
D
D030562:Databases, Protein; D008958:Models, Molecular; D009154:Mutation; D011489:Protein Denaturation / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
D011506:Proteins