Computational studies on the functional and structural impact of pathogenic mutations in enzymes

Abstract

Enzymes are critical biological catalysts involved in maintaining the intricate balance of metabolic processes within living organisms. Mutations in enzymes can result in disruptions to their functionality that may lead to a range of diseases. This review focuses on computational studies that investigate the effects of disease‐associated mutations in various enzymes. Through molecular dynamics simulations, multiscale calculations, and machine learning approaches, computational studies provide detailed insights into how mutations impact enzyme structure, dynamics, and catalytic activity. This review emphasizes the increasing impact of computational simulations in understanding molecular mechanisms behind enzyme (dis)function by highlighting the application of key computational methodologies to selected enzyme examples, aiding in the prediction of mutation effects and the development of therapeutic strategies.