Error in binding energy calculation of protein-peptide complex

Md Khabeer Azhar

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Jun 28, 2025, 3:04:17 AMJun 28

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Dear gmxMMPBSA team,

I am trying to calculate binding energy of protein-peptide complex, where i have created index group for peptide separately and protein group contain protein + peptide both. After running the command :

gmx_MMPBSA commands

Error:

File "/opt/miniconda3/envs/gmxMMPBSA/lib/python3.10/site-packages/GMXMMPBSA/utils.py", line 600, in res2map

for e in value['num']:

TypeError: string indices must be integers

My index.ndx: -cg 1 17 or 17 18 getting same error

Note that major changes are planned in future for trjconv, to improve usability and utility.

Will write xtc: Compressed trajectory (portable xdr format): xtc

Select group for output

Group 1 ( Protein) has 7766 elements

Group 17 ( protien) has 7766 elements

Group 18 ( peptide) has 148 elements

em.gro file format:

from 1 to 515 is my protein molecule and numbering starts again from 1 to 9 which is my peptides, I have created seperate index file for peptide by choosing atom selection like a 7619-7766 using em.gro file, because residue selection get residues of protein:

515HSD HA 7604 8.332 10.462 15.041

515HSD CB 7605 8.322 10.469 14.825

515HSD HB1 7606 8.245 10.451 14.747

515HSD HB2 7607 8.352 10.576 14.819

515HSD ND1 7608 8.545 10.361 14.884

515HSD HD1 7609 8.541 10.382 14.982

515HSD CG 7610 8.442 10.383 14.795

515HSD CE1 7611 8.634 10.280 14.823

515HSD HE1 7612 8.726 10.245 14.872

515HSD NE2 7613 8.596 10.247 14.701

515HSD CD2 7614 8.474 10.312 14.683

515HSD HD2 7615 8.419 10.302 14.591

515HSD C 7616 8.144 10.542 14.987

515HSD OT1 7617 8.175 10.663 15.006

515HSD OT2 7618 8.024 10.503 14.989

1PRO N 7619 6.873 5.413 4.623

1PRO H1 7620 6.838 5.358 4.700

1PRO H2 7621 6.793 5.464 4.588

1PRO CD 7622 6.927 5.322 4.517

1PRO HD1 7623 6.919 5.373 4.418

1PRO HD2 7624 6.873 5.226 4.513

1PRO CA 7625 6.981 5.504 4.671

1PRO HA 7626 6.965 5.512 4.778

1PRO CB 7627 7.112 5.434 4.626

1PRO HB1 7628 7.168 5.499 4.554

1PRO HB2 7629 7.178 5.414 4.713

1PRO CG 7630 7.073 5.303 4.556

1PRO HG1 7631 7.136 5.282 4.467

2nd part where my peptide is ending:

9PHE CB 7750 7.869 4.903 6.499

9PHE HB1 7751 7.924 4.872 6.407

9PHE HB2 7752 7.927 4.869 6.587

9PHE CG 7753 7.741 4.825 6.502

9PHE CD1 7754 7.750 4.689 6.466

9PHE HD1 7755 7.847 4.648 6.441

9PHE CE1 7756 7.636 4.608 6.458

9PHE HE1 7757 7.645 4.504 6.429

9PHE CZ 7758 7.511 4.662 6.489

9PHE HZ 7759 7.422 4.601 6.481

9PHE CD2 7760 7.615 4.876 6.540

9PHE HD2 7761 7.604 4.978 6.573

9PHE CE2 7762 7.501 4.795 6.531

9PHE HE2 7763 7.405 4.837 6.555

9PHE C 7764 8.011 5.103 6.479

9PHE OT1 7765 8.084 5.134 6.577

9PHE OT2 7766 8.051 5.103 6.359

516SOL OW 7767 0.228 0.621 0.094

516SOL HW1 7768 0.137 0.636 0.133

516SOL HW2 7769 0.220 0.611 -0.006

517SOL OW 7770 0.183 0.274 0.999

517SOL HW1 7771 0.225 0.228 1.077

517SOL HW2 7772 0.088 0.246 0.991

518SOL OW 7773 0.041 0.399 0.595

518SOL HW1 7774 -0.054 0.390 0.624

518SOL HW2 7775 0.055 0.346 0.511

519SOL OW 7776 0.574 1.310 1.209

519SOL HW1 7777 0.486 1.305 1.162

519SOL HW2 7778 0.592 1.404 1.237

520SOL OW 7779 1.583 1.521 0.703

520SOL HW1 7780 1.536 1.491 0.787

520SOL HW2 7781 1.516 1.529 0.629

I am attaching the pdb files dump from trajectories for your reference.

I look forward to your response at your earliest convenience.

HLA-DQ5_frm.pdb

mariosergi...@gmail.com

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Jun 28, 2025, 9:02:27 AMJun 28

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You must define one group for the receptor and another for the ligand, that is, one group for the protein and another for the peptide. In this case, since the receptor and ligand are both proteins, you must perform a splitch to separate them into groups. The sum of the total atoms in each group must equal the number of atoms in group 1 (Protein). This assumes the peptide is of protein origin.

Md Khabeer Azhar

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Jun 28, 2025, 9:10:49 AMJun 28

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I have done that but the total energy value turns out to be very high.

Delta (Complex - Receptor - Ligand):

Energy Component Average SD(Prop.) SD SEM(Prop.) SEM

-------------------------------------------------------------------------------

ΔBOND -0.00 4.44 0.00 0.06 0.00

ΔANGLE 0.00 6.52 0.00 0.09 0.00

ΔDIHED -0.00 3.86 0.00 0.05 0.00

ΔUB -0.00 1.38 0.00 0.02 0.00

ΔIMP -0.00 1.42 0.00 0.02 0.00

ΔCMAP 0.00 2.35 0.00 0.03 0.00

ΔVDWAALS -85.69 0.45 5.16 0.01 0.07

ΔEEL -132.29 10.94 34.72 0.15 0.49

Δ1-4 VDW 0.00 2.31 0.00 0.03 0.00

Δ1-4 EEL 0.00 6.38 0.00 0.09 0.00

ΔEGB 169.58 13.73 31.14 0.19 0.44

ΔESURF -12.79 0.09 0.54 0.00 0.01

ΔGGAS -217.98 11.37 36.36 0.16 0.51

ΔGSOLV 156.79 13.73 30.83 0.19 0.44

ΔTOTAL -61.19 17.82 7.15 0.25 0.10

is it ok to have such high binding energy between peptides and protein?

However, when I performed docking using Vina-GPU, the binding energy between the complex was −11 kcal/mol.

mariosergi...@gmail.com

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Jun 28, 2025, 12:12:07 PMJun 28

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1. With Vina, you obtain an estimated affinity value in the form of energy from a scoring function, which is empirical; therefore, this is not a reliable metric for estimating interaction energy.
2. The value obtained with gmx_MMPBSA (TOTAL) corresponds to the enthalpy, often known as the relative binding energy (the entropic component is neglected). The entropic component is normally positive, so the binding energy would be higher (lower in absolute terms).
3. It is known that PB-based methods can overestimate energy, which is why they are usually used for comparisons between similar systems, but not for estimating absolute binding energy. There are many more robust methods for this purpose.

Md Khabeer Azhar

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Jun 28, 2025, 1:42:18 PMJun 28

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Ok, Thank you so much

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