A LARGE-SCALE PROCESSING OF KINETIC DATA FILES WITH DERIVATION OF THEINHIBITORY CONSTANT K-I - AN APPLICATION TO PROLINE ISOMERASES

An integral system of algorithms (file preprocessor + the adapted KORE program + the Powell non-linear least-squares minimizer) named KINMIN is described. This system was applied to simultaneously process a lar ge number of kinetic data files for cis/trans isomerization of Xaa-Pro bonds in synthetic peptides catalysed by peptidylproline cis/trans is omerases which can be inhibited by nanomolar concentrations of the imm unosuppressive compounds cyclosplorin-A, FK506 or rapamycin. The syste m allows preprocessing of kinetics data files and derives from them th e first-order rate constants which are used to optimize the inhibitory constant K-i of each inhibitor. The KINMIN program may be also applie d to derive K-i for other sets of enzymes and their inhibitors.