Exploring the Alchemical Transfer Method
Published on April 27, 2023
Alchemical free energy calculations estimate differences in binding free energy between related ligands. They are used when a discovery team wants to rank changes within a molecular series using molecular simulation.
The Alchemical Transfer Method, or ATM, estimates relative binding free energies by swapping the positions of two ligands through a coordinate transformation. The calculation runs in a single solvent box and is implemented in the open source OpenMM molecular simulation package.
The method and its evaluation are described in the papers below. They define the systems, protocols, evaluation measures and reported results. We link to the complete studies because applicability depends on the molecular series and the declared evaluation domain.
- Wu, J. Z., Azimi, S., Khuttan, S., Deng, N., and Gallicchio, E. (2021). Alchemical transfer approach to absolute binding free energy estimation.
- Azimi, S., Khuttan, S., Wu, J. Z., Pal, R. K., and Gallicchio, E. (2022). Relative binding free energy calculations for ligands with diverse scaffolds with the alchemical transfer method.
- Sabanés Zariquiey, F., Pérez, A., Majewski, M., Gallicchio, E., and De Fabritiis, G. (2023). Validation of the Alchemical Transfer Method for the Estimation of Relative Binding Affinities of Molecular Series.