Unveiling the microcosm during enzymatic hydrolysis of lignocellulose: From the perspective of molecular dynamics...

Lignocellulose, the most abundant renewable carbon reservoir on Earth, holds critical importance for sustainable bioenergy and biomaterial production. Lignocellulose is composed of three polymers-cellulose, hemicellulose, and lignin-whose hierarchical organization and intermolecular interactions fundamentally govern the enzymatic saccharification efficiency of lignocellulosic biomass. Molecular dynamics (MD) simulations provide an efficient way to explore the interaction between enzymes and lignocellulose and have become a widely adopted research method in this field in recent years. This review systematically outlines current MD simulations methodologies, including a comparative analysis of widely used software platforms and force fields, evaluating their advantages and disadvantages in modeling lignocellulosic systems. Then, the basic structures of cellulose, lignin, and cellulase and their model-building strategies are introduced. Finally, the applications of MD simulations to enzyme-lignocellulose interactions are summarized, including the recognition, adsorption, and hydrolysis of cellulose by cellulase, the influence of lignin on cellulase activity, the interaction between lignin and cellulose, and the interactions involving hemicellulose and other components. By integrating methodological advances with representative case studies, this review provides practical guidelines for designing, validating, and interpreting MD simulations of lignocellulosic enzymatic hydrolysis, with the ultimate goal of enabling rational improvement of biomass deconstruction processes.