On Thu, Apr 08, 2021, Homeo Morphism wrote:
>
>Every ligand from the set is hydrophobic. Perhaps, due to this, every
>simulation ends up with the same result: ligand trying to lose its contact
>with solvent, after some random-walking, eventually enters the cavity on
>the receptor which leads straight to its orthosteric site and blocks it.
Is there any chance you are starting the ligands close to cavity it binds
to? That might make it less likely for some ligands to find an alternate
binding site (say on the other side of the protein) that in real life would
compete with the first binding site.
Also, it only seems that you are investigating "k_on", the ease at which
ligand binding takes place. Relative affinities are generally dominated by
differences in "k_off", i.e. how long it takes to get back out. Values of
k_on are often very similar, which is what you seem to be seeing. Values of
k_off can differ by orders of magnitude.
Is your experimental result dominated by kinetics or more by thermodynamics?
If it is the latter, that might also help explain what you are seeing.
....dac
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Received on Thu Apr 08 2021 - 05:30:04 PDT
