Computer automated structure evaluation (CASE): a study of inhibitors of the thermolysin enzyme.

The Computer Automated Structure Evaluation (CASE) program has been applied to the analysis of the inhibition of the thermolysin enzyme by derivatives of di- and poly-peptides. The inhibition constant ki, was used as a measure of the activity of the inhibitors. The program successfully identified molecular fragments relevant to the inhibitory activity of the peptides, without any assumption regarding the mechanism of inhibitory action. Utilizing these major fragments, Quantitative Structure Activity Relationship (QSAR) calculations were performed yielding a multiple linear regression equation for the prediction of inhibitory activity. A comparison of the conclusions reported in the literature regarding the structural features involved in the inhibition of thermolysin with the major fragments identified by the program is also made.