Inquiry about Unusual Electrostatic and Polar Solvation Energy Relationship in gmx_MMPBSA Calculation

[Jane]

Hello, 

 

 Hope this email finds you well. I am writing to seek your expertise regarding some unusual results I encountered while performing binding free energy calculations using gmx_MMPBSA for protein-protein interactions.

In my MM/GBSA decomposition analysis, I observed an unexpected relationship between the Electrostatic and Polar Solvation energy components that appears physically counterintuitive. Specifically, I'm seeing cases where:

- **Electrostatic energy** shows very favorable values (e.g., -190 kcal/mol)
- **Polar Solvation energy** shows nearly neutral values (e.g., -0.7 kcal/mol)
- Meanwhile, the **total binding energy** appears reasonable (approximately -58 kcal/mol)

This pattern seems to contradict the expected physical behavior where a highly favorable vacuum electrostatic interaction should be accompanied by a significant desolvation penalty (positive Polar Solvation energy).

## My Calculation Details:

**Input Parameters:**
```ini
&general
sys_name="Decomposition",
startframe=2001,
endframe=2501,
forcefields="leaprc.protein.ff14SB",
/
&gb
igb=2, saltcon=0.150,
/
&decomp
idecomp=2, dec_verbose=3,
print_res="within 4"
/

My Questions:

1. What might be causing this apparent discrepancy between the expected physical relationship and the calculated results?
2. What parameter adjustments would you recommend to obtain more physically reasonable results?

• Would switching to PB calculation be beneficial?
• Should I try different GB models (igb=5, 7, or 8)?
• Are there specific dielectric constant settings that might help?