So-called 'alchemical' binding free energy calculations use molecular simulations spanning between different thermodynamic states to compute binding free energies. Our previous work applied these techniques to compute absolute binding free energies in two model binding sites in T4 lysozyme. Here, we discuss more recent work on predicting binding free energies on a charged binding site in cytochrome C peroxidase, as well as ongoing work in binding sites of pharmaceutical relevance. A focus is on lessons learned and challenges facing these techniques in predictive applications.

Alchemical calculations of binding free energies from MD simulations

245th National Meeting (2013)

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