Dear Amber users,
I'm attempting to measure the binding free-energy of a protein-protein
complex. Ligand binding to each of the two protein subunits are assumed to
weaken the binding energy between them.
Thus, I performed 6 MD simulations of the complex with the two ligands, and
6 MD simulations without the ligands. All simulations are 50 ns long. MMPBSA
was then used on each of the simulations to measure the binding free energy
in the two cases. 500 frames from each of the simulations were used in the
MMPBSA calculation.
I'm seeking some advice in how to interpret the results I get here. Also,
does it make sense to include the ligand in the MMPBSA calculation.
The MMPBSA "setup" and results are listed below. They show a small decrease
in the binding energy upon ligand binding. However, the variation in each of
the measurements seems to be quite large.
Any help is greatly appreciated.
Kind regards,
Lars Skjaerven
MMPBSA setup:
=Case 1=
"Complex": protA+ligand+protB+ligand
"Ligand": protA+ligand
"Receptor": protB+ligand
=Case 2=
"Complex": protA+protB
"Ligand": protA
"Receptor": protB
The results of the calculations are as follows:
=Case 1=
1. DELTA G binding = -67.2979 +/- 9.0536
0.4049
2. DELTA G binding = -70.5699 +/- 11.1792
0.4999
3. DELTA G binding = -74.2973 +/- 12.5725
0.5623
4. DELTA G binding = -67.2641 +/- 9.4797
0.4239
=Case 2=
1. DELTA G binding = -79.1609 +/- 8.6845
0.3884
2. DELTA G binding = -81.9272 +/- 13.0194
0.5822
3. DELTA G binding = -101.2126 +/- 13.0454
0.5834
4. DELTA G binding = -73.0323 +/- 10.4127
0.4657
5. DELTA G binding = -84.3521 +/- 8.7197
0.3900
6. DELTA G binding = -68.2018 +/- 8.1628
0.3651
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Received on Thu Oct 14 2010 - 03:30:04 PDT
