On Tue, Aug 20, 2024, SUBHASMITA MAHAPATRA MAHAPATRA via AMBER wrote:
>
>I want to calculate free energy between a ligand and its receptor protein.
>but, the ligand is forming a covalent bond with the 46th serine residue of
>the receptor. While preparing .prmtop files for MMPBSA, the ligand file
>contains the ligand along with 46th serine and a void formation happens in
>the 46th position in the receptor file. I would like to know how to take
>care of this problem.
First: you don't say how you "prepared the .prmtop files". For the
situation you describe, it probably needs to be done "by hand", since MMPBSA
is not designed to handle covalent binding.
Second: think carefully about what you plan to do with any estimate you
obtain. Force field calculations do not know anything about the energies
of forming or breaking covalent bonds. You might be able to compute the
free energy difference between a model compound (containg serine + ligand)
and the full protein system. But: is that a number that could be compared
to experiment, or whose value would help you interpret things? The free
energy of a covalent binding event is often highly dominated by the bond
formation energy, so MMPBSA may not help much.
...dac
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Received on Tue Aug 20 2024 - 10:00:02 PDT
