On Thu, Mar 16, 2023, Mei Kevin via AMBER wrote:
>
>I am currently using the thermodynamic
>integration module implemented in AMBER 20 to calculate the absolute
>binding energy of a cation to a protein pocket. To achieve this, I am
>attempting to let one cation inside the pocket vanish while simultaneously
>letting the one in the bulk appear. I am using a harmonic potential to
>restrain the pocket-located ion and a softcore potential to smooth the van
>der Waals energy.
Just a aside here: you a basically trying to solve one issue (having a
non-zero charge change) by introducing a tough new problem: how to fully
sample the free energy contribution of the "bulk" ion that you are creating.
Rightly or wrongly, most Amber developers have decided that the new problem
is more likely to lead to problems (i.e. non-cancellation of effects on two
sides of a thermodyanmic cycle) than is accounting for background charge
effects (especially if the two sides of the cycle that need to cancel use
the same or similar box sizes.)
It's great that others are trying out various strategies, and advice and
experience from users is welcome (and has been showing up on the reflector.)
But it's worth knowing that Amber's alchemical codes have not really been
written with the sort of application you have in mind.
....good luck...dac
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Mar 20 2023 - 11:00:03 PDT
