[gmx-users] does gromac "mdrun" produce predicted 3d structure?

[Justin Lemkul]

On 1/22/16 8:05 AM, Arron Lacey wrote:
> Hi everyone - I have used I-TASSER to generate pdb files for missense SNPs. I
> understand there are some reservations about the accuracy of SNP structural
> changes by using homology based methods alone. Can GROMACS off anything better?
> I have used
>
> gmx mdrun <options>
>
> to calculate the energy minimization of the pdb files that I-TASSER outputs, but
> I want to know if mdrun can produce the predicted co-ordinates of the structure
> due to the SNP (if there is any change that is)?
>

There is no really simple answer to this, but here are a few things to consider. 
  GROMACS does not predict structures.  It calculates the physical forces on the 
given configuration according to whatever instructions you provide.  Energy 
minimization is certainly insufficient to establish whether or not your mutation 
is structurally reasonable.  You need actual (extensive) MD simulations to 
determine that.  More importantly, the quality of the simulation is only as good 
as the force field you apply for the simulation.  All force fields involve 
assumptions and have some inaccuracy.  So your ability to "predict" using 
GROMACS (I suggest you don't use that term in this context) is only as good as 
(1) the rigor of the method you apply via the MD and (2) the quality of the 
force field in discriminating subtle behaviors.

-Justin

> Also - does there a better way to embed a SNP in a wild-type pdb file for input
> to pdb2gmx?
>
> Thanks very much.

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

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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