Optimization of kinetic proofreading: A general method for derivation of the constraint relations and an exploration of a specific case

Abstract

We have previously presented a general cost-accuracy relationship for a broad class of kinetic proofreading mechanisms. In this paper we present a general matrix method, based upon classical enzyme kinetics, for the derivation of the constraint relation that characterizes specific proofreading mechanisms. For purpose of illustration we present the method in the context of a conventional Michaelis-Menten mechanism with side reactions. We then explore optimization of the general cost function under a variety of different constraints that may exist for such a mechanism. In this way we are able to contrast different perspectives on the optimization of enzyme design.