Alchemical Transformation for calculation of standard binding free energies

From: Cameron Grant (
Date: Wed Aug 05 2020 - 04:44:58 CDT

Dear List,

I am interested in calculating the binding free energy of Human Neutrophil Elastase in complex with a small tetra peptide using the alchemical transformation methodology in NAMD. I have attempted to follow the NAMD tutorial on the matter. I've been successful in setting up both the forward and backward simulations. I however, am confused as to how I complete the calculations of the integrals whereby, the conformation is constrained against the Euler angles, Polar angles, Euclidean distance etc. Is this where the normal simulations with no FEP simulation come into play as per the tutorial files? If so what post-simulation processing is required to get these values into a format that can then be used in the integrations to find their respective effect on deltaG? For example, I am confused as to how I calculate/find the variables such as uc which are used within the integrals to calculate Keq alch. Any advice you could provide toward my issue would be greatly appreciated and I look forward to hearing from you.

Kind regards,
Cameron Grant

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