AMBER Archive (2006)

Subject: Re: AMBER: single or dual topology for TI?

From: David Mobley (dmobley_at_gmail.com)
Date: Sat Oct 21 2006 - 14:17:50 CDT

Holly,

> I plan to use AMBER8 to set up some thermodynamic integration calculations for determining relative
> free energies of colchicine (a three-ring, 54 atom organic molecule) and various derivatives in water. I
> would like to know if the TI implementation coded in AMBER8 works better for single or
> dual topology TI. I am going to set up TI where an OCH3 group (all atom representation) on colchicine
> is mutated to an OH group, or as another example, to an OCH2CHCH2 group, and I was wondering if I
> should use dual or single topology perturbation. For example in the first case I gave of mutating OCH3
> to OH, should I change that C on colchicine into an H and the three H's into dummy atoms, or should I
> change all atoms in the CH3 group into dummy atoms and then also have a dummy atom on the
> colchicine that I change into an H? I've never done TI before, and it would be great to hear any advice
> you have on this.

My personal opinion is that deleting or inserting atoms is a lot more
"work" than any other kind of a transformation (in the sense that it
requires more sampling to get reliable results) so it is preferable to
do as few deletions/insertions as possible in any transformation.
Hence, I would do it by changing the CH3 into H (changing C->H and
deleting three hydrogens). The other important point is to make sure
you never have charges on atoms that are being deleted, so I usually
prefer to do a separate transformation to turn off charges on the
atoms I'm deleting before I do the deletion (i.e. first turn off the
charges on the H3).

Best wishes,
David Mobley
UCSF

> Thanks,
> Holly Freedman
> --
> Department of Physics, University of Alberta
> Edmonton CANADA
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