# [gmx-users] Re: FEP

Fabian Casteblanco fabian.casteblanco at gmail.com
Mon Oct 10 22:39:32 CEST 2011

```Thanks Michael for your help.  This really helps a lot.  Thank you!

On Mon, Oct 10, 2011 at 4:10 PM, Fabian Casteblanco
<fabian.casteblanco at gmail.com> wrote:
> 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
>

--
Best regards,

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

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