Hi Matt,
See below my comments/answers in red.
Taisung
Is option 3 to the gti_add_sc keyword the “fix” to the problem with alchemical transformations in AMBER reported in <
https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.8b04187> J. Phys. Chem. B 2017, 121 (20), 5151−5161? If so, how can I tell when I need to switch from the default option of gti_add_sc=1? Is there a reason why “3” is not the default?
Yes. Theoretically gti_add_sc>1 will give you right answers hence there is no reason to set 3 as the default. “1” is the default because it produces results similar to other implementations.
Also, if bonded terms that cross the softcore-common core boundary should be removed, why is the default to gti_bat_sc to retain all bonded terms? How can I tell when to change to option 1 or 2 for this keyword. (By the way, how does option 1—where the program decides what bonded terms to retain—work?)
Theoretically bonded terms can be all scaled or kept with some rules. When all of them are scaled, the simulation will be extremely difficult to converge and one needs to be very careful to handle this issue. The default behavior is NOT to scale any bonded term (similar to other implementations) to avoid user-errors. If you don’t understand the theoretic details, I suggest you use the default values. Or you can read this paper first <
https://doi.org/10.1021/acs.jctc.0c01328>
https://doi.org/10.1021/acs.jctc.0c01328
These questions are motivated by a large discrepancy I obtained when trying to compute the Delta_G for the W6F mutation in the Trp-cage peptide. I obtained a Delta_G of +7.4 kJ/mol, but the reported <
https://link.springer.com/protocol/10.1007/978-1-4939-8736-8_2> value is -4.29 kJ/mol. I equilibrated the initial and final states, and took 70 200-ps-equally spaced snapshots from each to initiate fast-growth transitions in the A->B and B->A directions, respectively. Each morphing simulation was 200 ps in the NPT ensemble. When I use the free energy estimators implemented in the PMX package, I obtain the below result. I’d greatly appreciate any thoughts/suggestions on what I’m doing wrong. I’m happy to provide more details if that’d be helpful.
Since different definitions and treatments of the SC regions will give different \Delta G values, it is not meaningful to compare \Delta Gs. You need to compare \Delta \Delta Gs where the SC internal energies are cancelled out.
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Tue Nov 08 2022 - 05:30:02 PST
