[gmx-users] how to fix error: Some of these results violate the Second Law of Thermodynamics

[Paul bauer]

Hello,

you'll need to check if you are properly sampling the different states 
in your simulations,  which should be possible by analyzing the 
histograms you can get from gmx bar -oh

Otherwise you'll need to check if your simulation parameters are 
realistic, as the program warns you :)

Cheers

Paul

On 13/02/2020 21:19, Sadaf Rani wrote:
> Dear Gromacs users
>
> I am doing free energy calculation of a ligand with protein. When I do gmx
> bar it gives me the following error:-
>
> Temperature: 298.15 K
>
> Detailed results in kT (see help for explanation):
>
>   lam_A  lam_B      DG   +/-     s_A   +/-     s_B   +/-   stdev   +/-
>       0      1    3.29  0.06    1.28  0.10    1.37  0.08    1.54  0.09
>       1      2    1.41  0.04    0.47  0.05    0.31  0.05    0.77  0.03
>       2      3    0.88  0.06    0.09  0.02    0.06  0.01    0.41  0.06
>       3      4    0.67  0.03   -0.01  0.03   -0.01  0.03    0.25  0.01
>       4      5    0.50  0.01    0.11  0.00    0.10  0.00    0.22  0.01
>       5      6    0.33  0.01   -0.04  0.01   -0.07  0.03    0.21  0.03
>       6      7    0.27  0.02    0.07  0.04    0.04  0.02    0.22  0.03
>       7      8    0.11  0.03    0.05  0.02    0.04  0.01    0.16  0.01
>       8      9    0.11  0.01   -0.09  0.02   -0.10  0.02    0.17  0.01
>       9     10    0.08  0.02    0.12  0.01    0.12  0.01    0.20  0.00
>      10     11   -0.04  0.03   -0.01  0.03   -0.01  0.03    0.18  0.01
>      11     12   -0.09  0.03    0.06  0.03    0.05  0.03    0.19  0.02
>      12     13   -0.02  0.03   -0.12  0.03   -0.12  0.03    0.23  0.01
>      13     14   -0.01  0.03    0.17  0.03    0.16  0.03    0.28  0.02
>      14     15   -0.06  0.03   -0.09  0.03   -0.09  0.03    0.25  0.01
>      15     16   -0.04  0.03    0.13  0.04    0.13  0.04    0.29  0.01
>      16     17   -0.15  0.03    0.04  0.01    0.04  0.01    0.24  0.01
>      17     18   -0.14  0.03    0.01  0.02    0.01  0.02    0.25  0.01
>      18     19   -0.07  0.03   -0.01  0.01   -0.08  0.02    0.27  0.01
>      19     20   -0.05  0.01    0.18  0.00    0.09  0.00    0.28  0.00
>
> WARNING: Some of these results violate the Second Law of Thermodynamics:
>           This is can be the result of severe undersampling, or (more likely)
>           there is something wrong with the simulations.
>
>
> Final results in kJ/mol:
>
> point      0 -      1,   DG  8.14 +/-  0.14
> point      1 -      2,   DG  3.50 +/-  0.09
> point      2 -      3,   DG  2.19 +/-  0.14
> point      3 -      4,   DG  1.66 +/-  0.07
> point      4 -      5,   DG  1.24 +/-  0.02
> point      5 -      6,   DG  0.83 +/-  0.02
> point      6 -      7,   DG  0.66 +/-  0.06
> point      7 -      8,   DG  0.28 +/-  0.08
> point      8 -      9,   DG  0.28 +/-  0.03
> point      9 -     10,   DG  0.19 +/-  0.05
> point     10 -     11,   DG -0.10 +/-  0.08
> point     11 -     12,   DG -0.22 +/-  0.07
> point     12 -     13,   DG -0.05 +/-  0.08
> point     13 -     14,   DG -0.03 +/-  0.08
> point     14 -     15,   DG -0.16 +/-  0.07
> point     15 -     16,   DG -0.10 +/-  0.07
> point     16 -     17,   DG -0.37 +/-  0.07
> point     17 -     18,   DG -0.35 +/-  0.08
> point     18 -     19,   DG -0.17 +/-  0.06
> point     19 -     20,   DG -0.13 +/-  0.02
>
> total      0 -     20,   DG 17.29 +/-  0.47
>
>
> I have read in the link that I should not have negative entropy values in
> my simulation
> https://www.mail-archive.com/gmx-users@gromacs.org/msg55772.html.
> Can anyone please suggest me what could be wrong during my simulation and
> how should I fix it?
>
> Thank you
> Sadaf Rani
> Ph.D. visiting student
> Lancaster University
> Uk


-- 
Paul Bauer, PhD
GROMACS Development Manager
KTH Stockholm, SciLifeLab
0046737308594