Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases

An additivity-based sequence to reactivity algorithm for the interaction of members of the Kazal family of protein inhibitors with six selected serine proteinases is described. Ten consensus variable contact positions in the inhibitor were identified, and the 19 possible variants at each of these po sitions were expressed. The free energies of interaction of these variants and the wild type were measured. For an additive system, this data set allo ws for the calculation of all possible sequences, subject to some restricti ons. The algorithm was extensively tested. It is exceptionally fast so that all possible sequences can be predicted. The strongest, the most specific possible, and the least specific inhibitors were designed, and an evolution ary problem was solved.