Hi! Maybe you should try steered MD or de umbrella sampling, given that you
have structures of the bound and unbound protein. Just a thought!
Regards!
Gera!
El lun., 20 de ene. de 2020 16:16, Homeo Morphism <homeo.morphizm.gmail.com>
escribió:
> There's a certain protein. When a ligand binds to it, it experiences
> massive confomational transition: its certain domain covers distance that
> is on the order of several dozens of angstroms and for some individual
> residues it's even more.
>
> PDB structures for both ligand-free and ligand-bound (that is after this
> massive conformational transformation has occurred) proteins are available.
> There's also a set of experimentally verified mutations that make this
> protein constitutively active.
>
> I've been trying to model the conformational transition of this
> constitutively active protein with molecular dynamics and I'm failing at
> it...
>
> First, I tried to use so to say ordinary molecular dynamics - tip3p water,
> NPT with Langevin thermostat, SHAKE enabled, 2 fs timesteps, etc. I got
> nothing, but perhaps this is expected.
>
> I then moved to accelerated MD, heating and cooling, just heating and
> keeping it at high temperature, etc. Nothing. My accelerated MD attempts
> are especially worthy of being mentioned: I was slowly raising boost with
> each restart and the boost got so high that secondary structures began to
> denature but there was no sign of the domain that is supposed to move even
> beginning to move.
>
> Has anyone tried something similar with AMBER?
>
> Is my failure simply due to my not having found the right parameters and
> modes of the simulation? There's still a replica exchange method that I
> haven't tried yet. Self-guided langevin, etc.
>
> Or are there some fundamental constraints that preclude these large
> transitions from being modeled?
>
> Any recommendations?
>
> I use pmemd.cuda and it delivers 100-150 ns per day on our GPUs for the
> protein in question, so it's not Anton 2, but we aren't slow either.
>
> Thanks.
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Jan 20 2020 - 11:30:02 PST
