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Abstract
Free energy calculations based on molecular dynamics simulations offer a quantitative assessment of biomolecule binding and stability. This chapter discusses accurately estimating the free energy differences employing nonequilibrium alchemy. We cover the theoretical background, technical aspects of free energy simulations, and practical frameworks of efficient simulation set-up. The chapter also details several examples of large-scale quantitative estimations of binding free energy, including protein-ligand, protein-protein, and protein-nucleic acid binding. Overall, we provide a comprehensive guide to state-of-the-art simulation methods for accurate free energy calculations in the field of molecular biophysics and computational chemistry.
