Conservative Motion Theory – Bio II Rational Enzyme Design via Conservative Flow Engineering

Abstract

We extend CMT–Bio I by developing a complete analytic framework for rational enzymedesign. Enzymatic catalysis is modeled as a conservative flow network acting on the reactionmanifold, where folded protein structures create reflection–positive Fredholm kernels thatcompress substrate motion. Here we show how to engineer such kernels: by controllinggeometric preorganization, electrostatic funnels, and transition–state zero structure, onecan construct artificial enzymes with arbitrarily specified catalytic activity. This yields aprincipled method for designing ultrafast biocatalysts, including de novo proteins, RNAenzymes, and nanoscale catalysts.