[gmx-developers] Free Energy Calculation

[Justin A. Lemkul]

As a preface, please note that the development list is not the appropriate forum 
for this question.  I am CC'ing this message to the gmx-users list.  Please post 
any future questions there.

Emanuel Birru wrote:
> Hi,
> 
>  
> 
> I am doing a partition coefficient of solute between 1-Octanol and water 
> using gromacs ffG53a6 force field. The first thing I have done is to 
> predict the Gibbs free energy of salvation of pentane (my solute) in 
> 1-Octanol by thermodynamics integration method using 16 λ (lambda) 
> values. The problem have stated on λ=0.6 and it is LINCS error which 
> says as follows:
> 
> Fatal error:
> 
> Too many LINCS warnings (1001)
> 
> If you know what you are doing you can adjust the lincs warning 
> threshold in your mdp file or set the environment variable 
> GMX_MAXCONSTRWARN to -1, but normally it is better to fix the problem
> 
> The atoms that make the problem are pentane atoms.
> 

And what parameters are you using for both pentane and octanol?  Have you 
validated that they should otherwise run stably?  LINCS warnings usually come 
from insufficient minimization and/or equilibration, i.e.:

http://www.gromacs.org/Documentation/Errors#LINCS.2fSETTLE.2fSHAKE_warnings

>  
> 
> I have put the parameter file that I am using on this link 
> http://hydra.pharm.monash.edu.au/md_project/production.txt
> 
>  
> 
> After I got the error I have tried to run it again by changing the time 
> step and the soft core value i.e sc_alpha and run three jobs independently
> 
> 1.       With 1fs time step and sc_alpha = 1.51
> 
> 2.       With 2fs time step changing sc_alpha to 0.5 and
> 
> 3.       With 1fs time step and 0.5 sc_alpha
> 
> The same problem happened for 2 and 3 but 1 works well, but the average 
> dVpot/d λ is not what I expected, its >+7. I could not figure it out 
> where exactly the problem is.
> 

Regarding values for sc_alpha, there are some helpful tips and discussion in the 
free energy tutorial, specifically in the section:

http://www.dillgroup.ucsf.edu/group/wiki/index.php?title=Free_Energy:_Tutorial#More_run_input_files

-Justin

>  
> 
> Thanks in advance for your advise.
> 
>  
> 
> Cheers,
> 
> Emanuel
> 
>  
> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================