MD simulation of two different complexes (dimer and oligomer complexes) of two proteins were performed using GROMACS and the binding energies of a specific interface (1000 snapshots) was calculated using g_mmpbsa tool. I found the drastic difference of binding energies. how to deal with that and especially how to deal with the positive binding energies (Gbind) ? The calculated binding energy components are given bellow. Please help..!
Dimer:
van der Waal energy = -174.820 +/- 0.731 kJ/mol
Electrostattic energy = -342.809 +/- 2.527 kJ/mol
Polar solvation energy = 576.248 +/- 4.012 kJ/mol
SAV energy = -145.755 +/- 2.195 kJ/mol
Binding energy = -87.349 +/- 3.663 kJ/mol
Oligomer:
van der Waal energy = -183.391 +/- 0.518 kJ/mol
Electrostattic energy = -280.516 +/- 1.539 kJ/mol
Polar solvation energy = 634.006 +/- 3.068 kJ/mol
SAV energy = -152.732 +/- 1.921 kJ/mol
Binding energy = 17.304 +/- 3.309 kJ/mol
1000 snapshots is an extremely small number: collect more snapshots (at least 10^6---collect them every, let's say, 10 MD steps). 1 MD simulation is not enough: run more MD simulations (at least 3). Calculate relative binding free energies of dimers and oligomers using free monomers in solution as the reference systems---but can this be done with MM-PBSA, i mean, can the explicit solvent be included in MM-PBSA free energy calculations?
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i am not an MM-PBSA user.
the simulations were run in triplicate for 100ns each and 1000 snapshots were considered for the computation of binding energy. No the solvents were excluded. only two proteins / domains were considered for computation.
Have you considered an alternative approach: using the key interface residues as a probe and calculating the free energies using Linear Interaction Energy (LIE) approach? With LIE, one can easily write energies every 10 MD steps and include the solvent effects explicitly . . .
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