Hi I'm confused with the output of mmpbsa. Can someone help me?

[mk_KIM]

I performed MD simulations of an antibody (Ab) and peptide complex using Gromacs. Chain A is the target peptide, while chains B and C are the antibody heavy chain (HC) and light chain (LC), respectively. I created an index for chains B+C and A, then calculated GB and DECOMP with gmx_mmpbsa.

I’m confused because the binding delta G is a small negative value (around -6), but the DECOMP results show overall residues within 10 Å have negative total energy contributions. Shouldn’t the sum of individual residue contributions equal the total binding energy?

Additionally, the interaction entropy graph shows sharp increases in steps. Does this indicate the system is becoming more disordered?

Finally is there any recommendation of an appropriate combination of forcefield and water model? I used ff99sb-ildn and TIP3P.

Thank you for any assistance!

 

[marioe911116]

Technically the sum of the contributions of all residues, not just a few selected ones, should be equal to the calculated energy. However, the decomposition methods aren't exact and should be considered more for relative comparisons of residues contributions rather than informing absolute values. The sharp increase in interaction entropy values means the interaction energy is not stable and hence interaction entropy probably is not a good fit in this case (more info here: https://pubs.acs.org/doi/full/10.1021/acs.jctc.1c00374). Finally, a good combination of force filed + water model as per Amber's manual is ff19SB with OPC (more info here: https://ambermd.org/doc12/Amber24.pdf page 32)