[gmx-users] FEP

[Fabian Casteblanco]

Hi all,

I have an additional question related to what Steven Neumann was
mentioning.  I actually have to do a molecule mutation.  I'm trying to
use Michael Shirts method  1) making small
changes 'alchemical' changes in the molecules and computing the free
energies by any method (BAR, TI, etc).  I'm specifically want to try
to use BAR at the end once I collect all the data.  This helped a lot
on clarification since it seemed that Justin's tutorial is essentially
a FEP except its using the BAR mathematical method for computing the
complete decoupling of the molecule rather than using the old FEP
mathematics of the exponential averaging formula.  So BAR is only
referring to the mathematical code used to calculate the overall free
energy for the FEP, correct?

My question is, for a mutation of a -CH3 group to a -H group, is it
better to simply run:
[+ from (Lambda=0 ,  R-CH3, full charges and interactions -STATE A)
--> (Lambda=1, R-CH, full charges and interactions -STATE B)]

OR

[1) from (Lambda=0 ,  R-CH3, STATE A : Charges and LJ Interactions: ON)
2)  (Lambda=?, -CH3 Charges: OFF ,LJ Interactions: ON and unmutated)
3)  (Lambda=?, R-CH3, -CH3 Charges: OFF ,LJ Interactions: OFF)
4)  (Lambda=?, R-CH3, -CH3 Charges: OFF ,LJ interactions: ON and Mutated to -H)
5)  (Lambda=1, R-CH3, -CH3  STATE B : Charges and LJ Interactions: ON)

Reason I'm asking is because when I try the first choice to do it
STATE A to STATE B in one step, when I reach Lambda=0.85 and above on
the NVT equilibration right after EM, I receive errors saying that
bonds are moving way to far off their constraints which leads me to
believe that the system is moving too far from where it was energy
minimized.  Errors such as:

Step 188, time 0.376 (ps)
LINCS WARNING
relative constraint deviation after LINCS:
rms 0.000017, max 0.000636 (between atoms 9 and 68)
bonds that rotated more than 30 degrees:
 atom 1 atom 2  angle  previous, current, constraint length
      9     68   31.2    0.1111   0.1110      0.1111

Step 188, time 0.376 (ps)  LINCS WARNING
relative constraint deviation after LINCS:
rms 0.000015, max 0.000531 (between atoms 9 and 68)
bonds that rotated more than 30 degrees:
 atom 1 atom 2  angle  previous, current, constraint length
      9     68   31.0    0.1111   0.1110      0.1111


**Please, if anybody can help, I would greatly appreciate it.  Thanks.
-- 
Best regards,

Fabian F. Casteblanco
Rutgers University --
Chemical Engineering
C: +908 917 0723
E:  fabian.casteblanco at gmail.com