[gmx-users] Most appropriate structure to compare to in g_rms

[Tsjerk Wassenaar]

Hey :)

For the fitting that is probably irrelevant. The motions of the side chains
at the surface are unlikely to affect the fit, because their mass is small
compared to the core of the protein and because there will probably be
compensating motions. A better reason for using only the backbone or
C-alpha atoms is that it's much cheaper (cost of fitting is linear in the
number of atoms) and because it doesn't matter much anyway.

Tsjerk


On Tue, Aug 19, 2014 at 1:49 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 8/19/14, 4:17 AM, Natalie Stephenson wrote:
>
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [
>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se] >on behalf of Justin
>>> Lemkul [jalemkul at vt.edu]
>>> Sent: 18 August 2014 17:47
>>> To: gmx-users at gromacs.org
>>> Subject: Re: [gmx-users] Most appropriate structure to compare to in
>>> g_rms
>>>
>>
>>  On 8/18/14, 9:41 AM, Natalie Stephenson wrote:
>>>
>>>> Hi all,
>>>>
>>>> This probably seems a really obvious question, but I'm struggling to
>>>> get my
>>>> head around it. I am performing simulations to determine the effect of
>>>> mutations on key regions of the protein. I have a crystal structure
>>>> which I
>>>> am using as the WT construct, and have performed homology modelling to
>>>> create
>>>> the point mutations of interest.
>>>>
>>>> I have used g_rms using the Production MD .tpr as the reference to look
>>>> at
>>>> the change in movement for key regions of the structure, comparing the
>>>> degree
>>>> of movement with the WT and mutated construct. Unfortunately, this does
>>>> not
>>>> necessarily tell me about changes occuring, for example, one key region
>>>> is
>>>> showing no change in RMSD however is displaced compared to that in the
>>>> WT.
>>>>
>>>
>>> Can you provide your exact command(s) and the groups chosen for fitting
>>> and
>>> output?  The outcome is highly dependent upon proper choices being made.
>>>
>>>
>> The commands I have been using are:
>> 1. g_rms -s prodMD.tpr -f prodMD.xtc -n index.ndx -tu ns -o
>> prodMD_RMSD.xvg (to compare to equilibrate structure)
>> 2. g_rms -s EM.tpr -f prodMD.xtc -n index.ndx -tu ns -o
>> prodMDtoEM_RMSD.xvg (to compare to crystal structure)
>>
>> In both cases I have been chosing protein for the least square fit and
>> then the specific region for the fit, though I'm not sure this is correct.
>> What is the best way of knowing which is the proper choice for this? Is
>> there any good resources I could access to read up on this?
>>
>>
> Fitting to the entire protein is a bit uncommon; fitting is almost always
> done to backbone or C-alpha groups, because for a well-folded protein, the
> structure should not change a whole lot.  If you fit to the whole protein,
> you're trying to fit against rapidly moving side chains, especially those
> on the surface whose motions are not necessarily functionally significant
> and may actually obscure detail.
>
> -Justin
>
>
>  Would it be better to use the WT EM.tpr as the reference structure for
>>>> everything (i.e. compare everything to the WT crystal structure)?
>>>> Obviously
>>>> these topologies will have slightly different numbers of atoms etc.
>>>> will this
>>>> be a problem?
>>>>
>>>>
>>> This will be a problem.  You can get around it, though, by using tpbconv
>>> (gmx
>>> convert-tpr in 5.0) to extract just backbone atoms from both .tpr files
>>> and
>>> trajectories.  If you don't, g_rms will complain about mismatching atom
>>> numbers
>>> or you will be mapping the wrong atoms in the trajectory since the two
>>> proteins
>>> have different numbers of atoms.
>>>
>>> Also note that g_rmsf is probably useful here, too, as you can get
>>> per-residue
>>> fluctuations and RMSD.
>>>
>>> -Justin
>>>
>>>
>> This is what I had thought - I'll definitely try using tpbconv to fit the
>> backbones and look into changes. Though some of the changes I am interested
>> in are the sidechain movements. I'll definitely try the g_rmsf for this.
>> Thanks so much for all the help!
>>
>> Natalie
>>
>>  --
>>> ==================================================
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>>
>>> Department of Pharmaceutical Sciences
>>> School of Pharmacy
>>> Health Sciences Facility II, Room 601
>>> 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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>>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 601
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
> --
> Gromacs Users mailing list
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-- 
Tsjerk A. Wassenaar, Ph.D.