[gmx-users] Re: decoupling charge while maintaining intramolecular potentials (chris.neale at utoronto.ca)

[Michael Shirts]

Hi, Chris-

I unfortunately can't be too much help, because my free energy
calculations are done through a modified version of Gromacs 3.1.4, and
I am currently working with Berk and Erik to get the important
modifications into the 4.0 branch.

> I am a new user of the free energy code. I am somewhat confused
> regarding the method that should be applied to decouple the long range
> interactions of the solvent from the solute while still maintaining
> intramolecular long-range interactions for the solute.

By long range interactions, you mean the ones outside the cutoff,
correct?  Because there's another set of difficulties dealing with the
ones that are shortange nonbonded interactions as well.  Could you
clarify?

> I was able to find some information in this thread:
> http://www.gromacs.org/pipermail/gmx-developers/2006-January/001498.html
> but it is still unclear to me.

I'm not surprised, it was unclear for us at the time as well :)

> I have reproduced the methane and tip3p energies of solvation based on
> the tutorial that is on the gromacs wiki. In this case, I simply
> assigned new charge values of 0 in the B state without making any
> special considerations for intramolecular O-H values. However, tip3p
> is rigid and perhaps maintaining the intramolecular q-q and LJ
> components is not essential in this case.

This is where I get confused -- are you talking about long range, or
any intramolecule interactions.  Certainly for methane and tip3p,
there aren't any, because all atoms are 1,3 neighbors.

> 1. Is it necessary to maintain the intramolecular long-range
> interactions for the solute while decoupling LJ or charge? If not
> absolutely required, does it affect the rate of convergence?

If you change the intramolecular nonbonded interactions, then you
would have to perform a second vacuum calculation in which you turn
them back on.   In terms of rates of convergence -- nobody really
knows.  If it's a intramolecular hydrogen bonding system, then turning
off the intramolecular interactions might be faster.

> 2. Is this already handled by the free-energy code?

I can't speak for the 4.0 code.  Berk was introducing nonbonded pair
terms such that these pair terms would overrule the 'alchemical'
transformation, resulting in unchanged intramolelcular nonbonded
interactions.  I actually don't know the current state of this change,
though.

> 3. If not, how might one go about doing this? My confusion with some
> additional [ pairs ] entry is how gromacs would get the right
> combination for lambda=0 and lambda=1 (not to mention intermediate
> states).

I'm a bit confused.  I would think that you would just want to set
them to the lambda=0 state, so that intramolecular interactions were
preserved.  Am I thinking of something different than you are?

Best,
Michael

~~~~~~~~~~~~~~~~~~~

Michael Shirts
Assistant Professor
Department of Chemical Engineering
University of Virginia
michael.shirts at virginia.edu
(434)-243-1821