[gmx-users] Comparing two Ptn-Ptn docking models

[Justin Lemkul]

On 3/10/15 9:34 PM, Diogo Martins de Sá wrote:
> Hi all,
>
>
> I have two proteins which I've docked and obtained two models, dock1 and
> dock2. Both corroborate, to some point, with literature experiments.
>
>
> I ran both models in a 76ns simulation, using 43a1 force field and PME.
>
>
> I have managed to map all salt bridges and their distances through the
> simulation (the intermolecular ones! between ARG, LYS, ASP and GLU), all
> hydrogen bonds and their percentage of appearance during the simulation
> (using one of Justin's scripts), and I also have all other contacts
> made between atoms and managed to make index group for all these stuff.
>
>
> In the .mdp I have specified Protein and Protein2 as energygroups.
>
>
>
> I have some ideas but I would like to know what would you guys recommend
> I do to infer which of the two models is most likely to be correct. What
> useful calculations should I look for? What energy terms (just Short
> range ones?)
>
>
> I guess the best thing to look for would be free energy of binding...
> I've been reading about it and came upon David Mobley and Justin's
> tutorial, which seem to work using PME (links at the end)
> When running the MDS of the ligand (in my case, also a protein) in
> water, should I start from scratch? Or can I use tbpconv to extract just
> the ligand out of my .tpr and then call mdrun -rerun with the new tpr
> and new coupling parameters? Would that satisfy any of the two
> tutorials?
>

Don't do an alchemical transformation with a protein.  Convergence is all but 
hopeless.  What you want is a PMF with umbrella sampling (I also have a tutorial 
for that).

-Justin

> thanks in advance
> Diogo
>
> Justin tutorial:
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy_old/index.html
>
> Mobley's:
> http://www.alchemistry.org/wiki/GROMACS_4.6_example:_n-phenylglycinonitrile_binding_to_T4_lysozyme
>
>
>
> Thanks in advance,
>
> Diogo
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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