Hello AMBER experts,
Instead of *non-covalent* ligands' relative binding energy, I am interested
in comparing the relative binding energy of two *covalent* ligands. These
two ligands LIG1 and LIG2 have the same covalent warheads to a residue,
with slightly different modification of two functional groups in the ligand
binding site (a bit far away from the covalent residue);
My question is: *is TI applicable for covalent ligands?* I am asking
because I know that I need to simulate both protein-ligand complex TI and
ligand-only TI to find the delta delta G for *non-covalent* ligands. I can
build the covalent bond between ligand and protein in AMBER following the
tutorial and run classical MD, but in ligand-only TI step, I am not sure
how.
If TI is not applicable for *covalent ligands*, any suggestions? If TI is
applicable, how should I proceed? My hypothesis is, I run TI covalent
ligand-protein complex, and then remove the covalent bond, run only
ligand-only TI to find the delta delta G, but the TI preparation step can
be tricky since the ligands' atom numbers are different in two systems:
ligand-protein complex system and ligand-only system.
Best,
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Received on Sun Sep 15 2024 - 08:30:02 PDT
