[gmx-users] [gmx-user] MD simulation of protein-ligand complex

[Quin K]

Thank you!
Let's say I extracted several snapshots of protein and docked with the
ligand separately and looked at the binding free-energy for each snapshot
with the same ligand, provided global properties are fine, would this help
in achieving stable complex during protein-ligand complex MD simulation?



On Tue, Dec 24, 2019 at 7:33 PM Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 12/24/19 12:47 PM, Quin K wrote:
> > Hi
> > Which of the following is the correct method to prepare a protein for
> > docking and then for protein-ligand complex MD simulation?
> >
> > 1. Do an MD simulation of protein for 100 ns and use the structure of
> > protein at 100 ns to do the protein-ligand MD simulation.
>
> There is no guarantee that the final snapshot is in any way
> representative of the rest of the simulation, so this is basically an
> arbitrary choice.
>
> > 2. Do an energy minimization of protein (like 5 ns) and use that
> structure
> > for MD simulation of protein-ligand complex.
>
> Energy minimization is not dynamical, so there are no time units. This
> is the more common approach (using an experimental structure) but is not
> necessarily representative of the dominant structure that exists in
> solution or that is receptive to ligand binding.
>
> The better approach is to choose a representative snapshot (or multiple)
> from a long MD simulation with very careful analysis of local (binding
> site) and global (overall structure) properties. Then you can make a
> robust choice for a docking target (or multiple, depending on what you
> find).
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Office: 301 Fralin Hall
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>
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