[gmx-users] residue titration w/ FEP

David L. Bostick dbostick at physics.unc.edu
Fri Aug 19 23:27:51 CEST 2005


I am calculating the free energy for deprotonating GLU-H --> GLU.   This is
an annihilation FEP exercise. State A is a regular GLUH residue, and State
B is the same residue with all bonded interactions the same, but all
non-bonded interactios turned off.  Also in state B, the mass of the proton
is zero.

I run into a problem at the very last window simulation at lambda=1 where
the proton has no mass.  Basically the proton moves around wildly w.r.t.
the residue and I get LINCS errors that cause the program to crash. I
imagine this is because there are no forces on the proton to keep it
tethered to the residue.

I imagine the solution is to mutate the proton to a dummy atom, but I'm not
sure how to do this. Could someone offer help / suggestions?


P.S. I suppose also that if I were to do a delta(delta G) calculation to do
a pKa shift or something, that I could in principle keep the mass of the
proton the same, since the thermodynamic cycle would cause the energy terms
in the reference state to drop out. However, I am still interested in
knowing about the particle annihilation problem.

David Bostick					Office: 262 Venable Hall
Dept. of Physics and Astronomy			Phone:  (919)962-0165
Program in Molecular and Cellular Biophysics
UNC-Chapel Hill
CB #3255 Phillips Hall				dbostick at physics.unc.edu
Chapel Hill, NC 27599	           		http://www.unc.edu/~dbostick

More information about the gromacs.org_gmx-users mailing list