[gmx-users] "B" state for free energy corrupts minimization?

[mernst at tricity.wsu.edu]

I am attempting to perform a free energy simulation that involves the
transformation of the lesioned DNA base 8-oxoguanine to guanine. Before I
set up the B state in my .itp file, I was able to simulate 8-oxoguanine
with MD and its behavior looked to be in reasonable agreement with
simulations I have performed in another package.

Now that I have defined B-state parameters, MD and even energy
minimization give strange and undesirable results, even before I begin the
free energy calculations or set lambda to a non-zero value.

I've narrowed it down to a simple test case where I supply a B state for
just one atom.

If I use this line in my .itp file, which changes nothing between A and B,
the energy minimization gives a reasonable-looking structure:

46 amber99_35 2 8oG  N7   46   -0.5129    14.01   amber99_35 -0.5129 14.01

This is what the output looks like:

http://www.sciencemadness.org/scipics/goodtrimer.png

If I use this line, using a different atom type in the B state,

46 amber99_35 2 8oG  N7   46   -0.5129    14.01   amber99_36 -0.5129 14.01

the minimization gives me a hydrogen that sticks out at a strange angle:

http://www.sciencemadness.org/scipics/badtrimer.png

The amber99_35 atom is AMBER type NA, corresponding to sp2 N in 5
memb.ring w/H atom (HIS). The amber99_36 atom is AMBER type NB,
corresponding to sp2 N in 5 memb.ring w/LP (HIS,ADE,GUA). In the A state
there is a hydrogen that becomes a dummy in the B state, so I would like
to go from NA to NB. The AMBER force field port to Gromacs is from the
Pande group.

I cannot figure out why this effect shows up when lambda=0, and how I
might set up the free energy simulation so that it is not horribly
distorted and prone to crashing in the equilibrium period.

Matt Ernst
Washington State University