Re: [AMBER] Is there any sense in even trying to model large conformational dynamics with molecular dynamics?

From: Gerardo Zerbetto De Palma <>
Date: Mon, 20 Jan 2020 16:24:30 -0300

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!

El lun., 20 de ene. de 2020 16:16, Homeo Morphism <>

> 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.
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Received on Mon Jan 20 2020 - 11:30:02 PST
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