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Title: Prediction of Protein Thermostability
P63
Hoppe, C.; Schomburg, D.

ch.hoppe@smail.uni-koeln.de
Department of Biochemistry University of Cologne

A distance- and direction-dependent knowledge-based potential [1] was developed and evaluated for the prediction of protein thermostability. It provides a fast estimate of the thermostabilic effect of a single mutation in a protein. The potential consists of two parts, the pairwise energy function based on a distance- and direction-dependent atomic description of the environment with five different atom types [2] and a torsion angle energy function [3].
First a training set of 10 protein with 528 single mutations was used to find and optimize the best set of parameters. The resulting potential function was then tested using a blind test mutant database selected from ProTherm [4,5] consisting of 29 proteins with 908 single mutations. The best correlation coefficient obtained between the experimental data and the computation for the training set is 0.75 with 76% correct predicted to be either stabilizing or destabilizing. For the test set the correlation coefficient is 0.4 with 75% correct predicted. The best sensibility achieved for the training set was up to 83%.
The present potential function creates a profile of possible candidates for point mutations and can act as a reliable guide in protein engineering and enzyme optimisation.
[1] Sippl, M., J. (1993), Boltzmann's principle, knowledge-based mean fields and protein folding. An approach to the computational determination of protein structures. J. Comput. Aided Mol. Design 7, 473-501.
[2] Dengler, U. (1998), PHD-Thesis, Braunschweig.
[3] Leven, O. (1999), PHD-Thesis, Köln.
[4] Gromiha, M., M., An, J., Kono, H., Oobatake, M., Uedaira, H. & Sarai, A. (1999), ProTherm: thermodynamic database for proteins and mutants. Nucl. Acids Res. 27, 286-288.
[5] Gromiha, M., M., An, J., Kono, H., Oobatake, M., Uedaira, H., Prabakaran, P. & Sarai, A. (2000), ProTherm, version 2.0: thermodynamic database for proteins and mutants. Nucl. Acids Res. 28, 283-285.