Similarity study of serine proteases inhibitors.

Two-dimensional structural similarity calculations have been applied to estimate binding affinities of serine proteases inhibitors. 1103 trypsin binders, 1268 thrombin binders and 714 fXa binders have been used to compare experimental and predicted data. The predictions generally provide reasonable estimates of the observed binding affinities. The accuracy of the predictions depends on the size of the dataset, but not dramatically. The accuracy also depends on the number of similar structures used to make the calculations, with a number from 3 to 6 usually being optimal. The binding affinity is noticeably more sensitive to the inhibitor structure in the case of fXa relative to thrombin.