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<div>Dear A.S. Lacey,</div>
<div> </div>
<div>Along the lines of Justin's answere, you need to perform more complicated simulations. I would suggest the 54a7 (partial atom) or CHARM36 (all atom) force fields, and add solvent and ions in a simulation box. Once in equilibration, your structure should mimic something like an NMR structure (100 pdb files with slightly different position/structure over time), with slight variations due to temperature and (solvent/neighboring) enviornment. Following one of the simple online tutorials would show you how to set up the simulation...</div>
<div> </div>
<div>Stephan L. Watkins, PhD</div>
<div> </div>
<div>Message: 1<br/>
Date: Fri, 22 Jan 2016 13:05:31 +0000<br/>
From: Arron Lacey <a.s.lacey@swansea.ac.uk><br/>
To: <gromacs.org_gmx-users@maillist.sys.kth.se><br/>
Subject: [gmx-users] does gromac "mdrun" produce predicted 3d<br/>
structure?<br/>
Message-ID: <56A2291B.4010102@swansea.ac.uk><br/>
Content-Type: text/plain; charset="utf-8"; format=flowed<br/>
<br/>
Hi everyone - I have used I-TASSER to generate pdb files for missense<br/>
SNPs. I understand there are some reservations about the accuracy of SNP<br/>
structural changes by using homology based methods alone. Can GROMACS<br/>
off anything better? I have used<br/>
<br/>
gmx mdrun <options><br/>
<br/>
to calculate the energy minimization of the pdb files that I-TASSER<br/>
outputs, but I want to know if mdrun can produce the predicted<br/>
co-ordinates of the structure due to the SNP (if there is any change<br/>
that is)?<br/>
<br/>
Also - does there a better way to embed a SNP in a wild-type pdb file<br/>
for input to pdb2gmx?<br/>
<br/>
Thanks very much.<br/>
<br/>
<br/>
------------------------------<br/>
<br/>
Message: 2<br/>
Date: Fri, 22 Jan 2016 08:13:13 -0500<br/>
From: Justin Lemkul <jalemkul@vt.edu><br/>
To: gmx-users@gromacs.org<br/>
Subject: Re: [gmx-users] does gromac "mdrun" produce predicted 3d<br/>
structure?<br/>
Message-ID: <56A22AE9.3010706@vt.edu><br/>
Content-Type: text/plain; charset=windows-1252; format=flowed<br/>
<br/>
<br/>
<br/>
On 1/22/16 8:05 AM, Arron Lacey wrote:<br/>
> Hi everyone - I have used I-TASSER to generate pdb files for missense SNPs. I<br/>
> understand there are some reservations about the accuracy of SNP structural<br/>
> changes by using homology based methods alone. Can GROMACS off anything better?<br/>
> I have used<br/>
><br/>
> gmx mdrun <options><br/>
><br/>
> to calculate the energy minimization of the pdb files that I-TASSER outputs, but<br/>
> I want to know if mdrun can produce the predicted co-ordinates of the structure<br/>
> due to the SNP (if there is any change that is)?<br/>
><br/>
<br/>
There is no really simple answer to this, but here are a few things to consider.<br/>
GROMACS does not predict structures. It calculates the physical forces on the<br/>
given configuration according to whatever instructions you provide. Energy<br/>
minimization is certainly insufficient to establish whether or not your mutation<br/>
is structurally reasonable. You need actual (extensive) MD simulations to<br/>
determine that. More importantly, the quality of the simulation is only as good<br/>
as the force field you apply for the simulation. All force fields involve<br/>
assumptions and have some inaccuracy. So your ability to "predict" using<br/>
GROMACS (I suggest you don't use that term in this context) is only as good as<br/>
(1) the rigor of the method you apply via the MD and (2) the quality of the<br/>
force field in discriminating subtle behaviors.<br/>
<br/>
-Justin<br/>
<br/>
> Also - does there a better way to embed a SNP in a wild-type pdb file for input<br/>
> to pdb2gmx?<br/>
><br/>
> Thanks very much.<br/>
<br/>
--<br/>
==================================================<br/>
<br/>
Justin A. Lemkul, Ph.D.<br/>
Ruth L. Kirschstein NRSA Postdoctoral Fellow<br/>
<br/>
Department of Pharmaceutical Sciences<br/>
School of Pharmacy<br/>
Health Sciences Facility II, Room 629<br/>
University of Maryland, Baltimore<br/>
20 Penn St.<br/>
Baltimore, MD 21201<br/>
<br/>
jalemkul@outerbanks.umaryland.edu | (410) 706-7441<br/>
<a href="https://3c.gmx.net/mail/client/dereferrer?redirectUrl=http%3A%2F%2Fmackerell.umaryland.edu%2F%7Ejalemkul" target="_blank">http://mackerell.umaryland.edu/~jalemkul</a><br/>
<br/>
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