Dear Amber users and developers,
I have a question about how to prepare dual-topology file for TI
simulation when converting charge is involved in the calculation of
relative binding free energy of protein mutation.
For instance, I'm now trying to mutate an Asp to Ala, which means the
charge of the TI region is converted from +1 to 0. I find that in some
paper, the authors will simultaneously change a WAT to Na+ when mutating
the amino acids.
I was wondering how I can get the dual-topology structure with the above
method if I'm using timerge module in Parmed. It always gives me error
messages that I can only merge adjacent residues. Because the WAT lines
will always be put at the end of the pdb file including both wild-type and
mutant protein. It's always very far away from the wild type, mutants, and
chosen Na+ I'm going to merge.
For instance, residue :1-10 is TI region 1 (chain with Asp), :11-20 is TI
region 2 (chain with Ala), :21 is Na+ (will disappear in the end state),
:22-100 are other chains, :101-200 is WAT. The WAT I choose to appear in
the end state is residule :101 that is definitely not adjacent to res :1-21.
Thank you for taking the time to read this email!
Best,
Fanyu
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Received on Mon Mar 27 2023 - 01:30:02 PDT
