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.