[Question]: How to avoid high standard deviation in energy values

[gayatripanda5]

I used gmx_MMPBSA for calculating the binding free energy between RNA and protein for 2500 frames using 5ns of trajectory as input. PBC was removed and the trajectory was fitted. The command used was

nohup mpirun -np 16 gmx_MMPBSA MPI -O -i mmgbsa.in -cs sys.pdb -ci prot_rna_dna.ndx -cg 1 12 -ct md_0-500ns_norest-5f9r-nomg-compact-nopbc_455-500ns_fit.xtc -cp topol.top &

mmgbsa.in file

&general sys_name="Prot-DNA" startframe=1 endframe=100 PBRadii=4 forcefields="oldff/leaprc.ff99SB" / &gb igb=8, saltcon=0.150, intdiel=10 / &decomp idecomp=2, dec_verbose=3, print_res="within 3" /

The command ran successfully. But the output that I got was

It shows a very high standard deviation. I initially ran it with less number of frames (100 frames) the output was giving std dev around 1894. I thought increasing the number of frames can reduce the std dev. But, the output didn't change much. Please suggest how can I reduce this value.

[Valdes-Tresanco-MS]

This is probably because your system is highly unstable. Check the RMSD of the system and make sure that you have completely removed the PBC and that your system is completely stable.

[gayatripanda5]

The backbone RMSD of the input trajectory part.

yes, PBC was removed using -pbc mol flag. snapshot of complex after removing water and ions

[Valdes-Tresanco-MS]

Certainly, the average RMSD is not that large considering the system characteristics. However, the variation in small windows is considerable, which is most likely due to the RNA and DNA fragments being less compact. Can you attach the output file for review? I believe that RNA and DNA molecules have an important weight in these results since the predominant contributions are EEL and EGB.

[gayatripanda5]

Sure, The output dat file is attached below.

On Wed, May 11, 2022 at 12:52 AM Mario Sergio Valdés Tresanco < @.***> wrote:

Certainly, the average RMSD is not that large considering the system characteristics. However, the variation in small windows is considerable, which is most likely due to the RNA and DNA fragments being less compact. Can you attach the output file for review? I believe that RNA and DNA molecules have an important weight in these results since the predominant contributions are EEL and EGB.

— Reply to this email directly, view it on GitHub https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA/issues/227#issuecomment-1122775204, or unsubscribe https://github.com/notifications/unsubscribe-auth/AQSH3U7L6AZ3R5DNLN53YKDVJKZQPANCNFSM5VSKIUTA . You are receiving this because you authored the thread.Message ID: @.***>

-- Gayatri Panda PhD19206 (Computational Biology)

[Valdes-Tresanco-MS]

Closed due to inactivity. In summary: In these cases, it is expected that these methods considerably overestimate the energy for systems with these characteristics. Also, due to the system's molecular nature and its flexibility, a high SD should be expected. You should carefully consider whether these methods are suitable for the system under study and the objective of your work.