Molecular modelling and free-energy calculations of protein-ligand binding

Computational modelling of the structure and thermodynamics of microscopic models provides a valuable tool for research on the molecular mechanisms of biochemical processes and on the reactivity of physiologically active compounds. The review concerns methods of free-energy calculations of equilibrium systems, including various techniques developed to improve the accuracy and efficiency of computations. Calculations of the binding thermodynamics for model proteinligand complexes are illustrated taking bacteriophage T4 lysozyme and beta-trypsin as model proteins. The role and potential of molecular modelling methods in drug design are discussed.