I’ve been trying to work out the binding energy of a homodimer, with 2 ligands and 2 water molecules (one per subunit).
I’ve generated two independent 100 ns trajectories.
I calculated the binding energy using the following input script
Input file for running PB and GB
&general
strip_mask = :WAT,Na+,&!:271-272
endframe=10000, verbose=1, interval=20,
# entropy=1,
/
&gb
igb=2, saltcon=0.100
/
&decomp
idecomp=1,
dec_verbose=1,
/
271 and 272 are the said two water molecules. They do not exchange with bulk solvent (occupancies > 85%)
In both cases mmpbsa.py.MPI through WARNINGS
GENERALIZED BORN:
WARNING: INCONSISTENCIES EXIST WITHIN INTERNAL POTENTIAL
TERMS. THE VALIDITY OF THESE RESULTS ARE HIGHLY QUESTIONABLE
the origin of these warning as it has been discussed previously in the list and my understanding is that they are not deemed important for single trajectories.
Differences (Complex - Receptor - Ligand)
DIHED 0.0001 0.0054 0.0002
DIHED 0.0000 0.0056 0.0003
(For BOND and ANGLE) the corresponding differences are zero.
BINDING ENERGY RESULTS OBTAINED
For trajectory 1, the binding energy = -54 kcal/mol
For trajectory 2, the binding energy = -47 kcal/mol
I stripped the water molecules and generated new topologies with ante-mmpbsa.py
I run mmpbsa.py using the same script as above with the only difference that the strip_mask was quoted out.
For trajectory 1, the binding energy = -49 kcal/mol
For trajectory 2, the binding energy = -37 kcal/mol
I don’t think these discrepancies are due to the water molecules, (1) because they are not at the binding interface although they do form h-bonds with the ligands part of which is at the binding interface and (2) because mmpbsa-decomp gives
for water1 -0.14 kcal/mol (trajectory 1); -0.22 kcal/mol (trajectory 2) &
for water2 —0.03 kcal/mol (trajectory 1); -0.11 kcal/mol (trajectory 2)
I’d appreciate any suggestions explaining this behaviour.
Many thanks in advance
George
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Received on Mon Mar 21 2016 - 10:30:04 PDT
