GROMACS modification: Yes/No
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I would like to calculate the absolute binding free energy of ligand-protein complex with alchemical method following the tutorial I found at:
However, this tutorial mentions that the net charge of a ligand can introduce artifacts which can be corrected with Rolin’s methods:
GJ Rocklin, DA Mobley, KA Dill, PH Hünenberger. Calculating the binding free energies of charged species based on explicit-solvent simulations employing lattice-sum methods: An accurate correction scheme for electrostatic finite-size effects. J. Chem. Phys. 139, 184103 (2013)
The above Rolin’s paper introduced the equations and algorithms. However, I am not good at math and I can hardly understand them.
Unfortunately, my ligand does has a net charge of -1. My questions are whether the corrections are necessary for calculation the absolute binding free energy when the ligand has a net charge? If yes, is there any simple tutorial that introduce the steps, commands and scripts for the correction procedure?