New paper in JCTC

Congratulations to Ben Irwin for the just accepted manuscript in JCTC. This paper entitled “Estimating Atomic Contributions to Hydration and Binding using Free Energy Perturbation” introduces formulae which when combined with a molecular dynamics free energy perturbation (FEP) simulation give an estimate of the contribution to a free energy change from each atom in the system. The formulae in the document are fully derived from the Zwanzig equation and the assumption that the system energy and free energy change can be split into contributions from each atom in the system. We apply the formulae to two systems, the calculation of the hydration free energy of a caffeine molecule and the calculation of the binding free energy of lopinavir to human immunodeficiency virus type-1 protease (HIV-1P). The results give a quantitative estimate which atoms in the respective molecules are strong contributors to the hydration/binding and which parts of the molecules are neutral or unfavourable. The paper has significant potential in the field of drug discovery as this method can be used as a tool to understand and improve the binding of ligands to targets. This method will also be of interest to any field of chemistry or physics which employs molecular dynamics simulations to measure free energy changes.

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