A Computational Framework for Linking Active Site Dynamics to Enzyme Promiscuity

Why do some enzymes perform only one reaction, while others quietly catalyse many?For decades, scientists have suspected that protein motion holds the answer; but attempts to link flexibility to function have remained frustratingly imprecise.This book offers a decisive shift in perspective.Rather than treating enzymes as whole, moving objects, A Computational Framework for Linking Active-Site Dynamics to Enzyme Promiscuity focuses attention where catalysis actually happens: the active site. Through large-scale molecular dynamics simulations and rigorous statistical analysis across diverse enzyme classes, the author introduces the Active-Site Flexibility Index (AFI) - a quantitative framework that isolates local dynamic tolerance within catalytic microenvironments. By demonstrating that AFI consistently outperforms traditional flexibility metrics in predicting substrate breadth, this work resolves a long-standing contradiction in computational enzymology.