Maybe the question was silly or I failed to communicate it correctly
What I’m trying to establish is whether ligand binding favours or disfavours binding of two chains of a homodimer.
Assuming two consecutive MD simulations involving:
1. A homodimer (chainA-chainB)
2. the same homodimer plus ligand X (chainA-X-chainB-X)
and treating chainA of the homodimer as the receptor and chainB as ligand would it be legitimate to assume that dimerisation is favoured if deltaG (chainA-X-chainB-X) < deltaG (chainA-chainB) ?
The second question is whether stripping the ligand from (2) would lead to perturbations such that a comparison of deltaGs (chainA-chainB) from the two trajectories is meaningless.
> On 20 May 2015, at 14:09, George Tzotzos <gtzotzos.me.com> wrote:
>
> I’ve run 3 consecutive MD simulations of 100ns each. A summary of delta-G total obtained by MMGBSA is given below.
>
> 1. homodimer. One of the chains treated as receptor the other as ligand. delta-G total -29kcal/mol
> 2. homodimer + 2 ligands (a & b). Used ante-mmpbsa.py to strip ligands (a & b) and generate topologies for chainA( to be treated as receptor) and chainB(to be treated as ligand). delta-G total -24kcal/mol
> 2. homodimer + 2 ligands (c & d). Repeated method used in 2. above. delta-G total -40 kcal/mol
>
> Clarification: single trajectories were used.
>
> Is such variation in delta-G total for binding of chainA to chainB to be expected? Is this due to perturbations upon ligand binding. Similar variation in delta-G was observed for binding of ligands to the dimer and the same ligands to the monomer (DIFFERENT MD runs)
>
> My objective is to determine whether the ligands stabilise or not dimer formation. Is the approach described above suitable for the purpose?
>
> Thank you in advance for any comments/suggestions
>
> Regards
>
> George
>
>
>
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Received on Wed May 20 2015 - 12:00:03 PDT
