[gmx-users] RMSF started increasing after 60 ns simulation

Wed Apr 11 16:44:29 CEST 2018

Thank you Justin :)
I wonder what is your strategy when considering what criteria could be used
for determining convergence of the simulation?
Ming

On Wed, Apr 11, 2018 at 10:30 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 4/11/18 10:26 AM, MD wrote:
>
>> Thank you Justin. Two quick questions (learning questions :))
>> 1. How do I apply several invocations of trjconv, (a quick guide would be
>> appreciated)
>>
>
> http://www.gromacs.org/Documentation/Terminology/Periodic_
> Boundary_Conditions#Suggested_trjconv_workflow
>
> If I had $0.10 for every time I posted that link, I could fund my summer
> salary... :)
>
> 2. Several literature used only 90-100 ns time window for RMSF analysis in
>> a 100ns run. Does that mean the later the time window is the more value of
>> RMSF it has?
>>
>
> Whenever a given time frame has been chosen for a particular analysis, it
> should be accompanied by an explanation of why that time frame was chosen.
> Is it because the authors believed the simulation did not converge until 90
> ns, and therefore they discarded 0-90 ns and only analyzed from 90-100 ns?
> That may be the case, but for a slow-converging system, I would expect the
> simulation to be run much longer to collect more data. 10 ns is not much
> time at all for anything useful.
>
> RMSF is particularly sensitive to equilibration; the initial frames in
> unrestrained MD are often not valid to include in this analysis, but one
> should consider very carefully what criteria are being used for determining
> convergence of the simulation. No one quantity will tell you this, even if
> it is aesthetically pleasing.
>
> -Justin
>
> Thanks again,
>> MD
>>
>> On Wed, Apr 11, 2018 at 10:17 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>
>>> On 4/11/18 10:16 AM, MD wrote:
>>>
>>> Hi,
>>>>
>>>> I wouldn't do cherry-picking. I am just confused how I can trust the
>>>> data
>>>> if the RMSD goes crazy in that range? Also based on the command I used I
>>>> think the PBC has been taken care of, please correct me if I am wrong :)
>>>>
>>>> And It would be very interesting, if the RMSF of wild type started
>>>> fluctuating after 70 ns for real.
>>>>
>>>> Also, yes you are right, this is a single run and I will need to
>>>> replicate
>>>> the simulation for several times. At the mean time I  would really like
>>>> to
>>>> learn how I can make a judgement which ranges of data I could use for
>>>> the
>>>> analysis :)
>>>>
>>>> The best tool you have is your eyes. Watch the trajectory. Understand
>>> what
>>> is happening during the time points for which the data behave very
>>> differently. Maybe something interesting is happening and you need to
>>> consider it. Maybe your PBC treatment is inadequate (often you need
>>> several
>>> invocations of trjconv to get things right, very few cases allow you to
>>> use
>>> a single, magic command).
>>>
>>>
>>> -Justin
>>>
>>> Thank you,
>>>
>>>> MD
>>>>
>>>> On Wed, Apr 11, 2018 at 10:08 AM, Justin Lemkul <jalemkul at vt.edu>
>>>> wrote:
>>>>
>>>>
>>>> On 4/11/18 10:04 AM, MD wrote:
>>>>>
>>>>> Hi,
>>>>>
>>>>>> Yes I am comparing the trajectories side by side and I ran a RMSD of
>>>>>> wild
>>>>>> type too.
>>>>>> I looked at the RMSD of wild type and it looks like it became unstable
>>>>>> after 70ns. In this case the only approach is to compare the
>>>>>> trajectories
>>>>>> in time windows before 70ns. Would that be right?
>>>>>>
>>>>>> I'd argue that that's cherry-picking, taking preferable data and
>>>>>>
>>>>> ignoring
>>>>> the real outcome. If the protein structure goes haywire (and it really,
>>>>> truly isn't a PBC effect, which it is in about 9 out of 10 cases...)
>>>>> then
>>>>> you should investigate what's going on. Maybe the .mdp settings are
>>>>> incorrect and causing the model physics to break down. Maybe the force
>>>>> field you chose is not sufficiently accurate for simulating the system.
>>>>> Is
>>>>> the behavior reproducible across multiple simulations, or are you
>>>>> looking
>>>>> at an outlier?
>>>>>
>>>>>
>>>>> -Justin
>>>>>
>>>>> Thank you,
>>>>>
>>>>> MD
>>>>>>
>>>>>>
>>>>>> On Wed, Apr 11, 2018 at 9:42 AM, Justin Lemkul <jalemkul at vt.edu>
>>>>>> wrote:
>>>>>>
>>>>>>
>>>>>> On 4/11/18 9:41 AM, MD wrote:
>>>>>>
>>>>>>> Hi Justin,
>>>>>>>
>>>>>>> This was the command I used for both wild type and mutant. I wonder
>>>>>>>> if
>>>>>>>> you
>>>>>>>> could think of any reason that made only the wild type have the PBC
>>>>>>>> effects?
>>>>>>>>
>>>>>>>> gmx trjconv -s md.tpr -f md.xtc -o md_noPBC.xtc -pbc mol -ur compact
>>>>>>>>
>>>>>>>> Visualize each trajectory as Mark suggested.
>>>>>>>>
>>>>>>>> -Justin
>>>>>>>
>>>>>>>
>>>>>>> Thank you,
>>>>>>>
>>>>>>> MD
>>>>>>>
>>>>>>>> On Wed, Apr 11, 2018 at 9:23 AM, Justin Lemkul <jalemkul at vt.edu>
>>>>>>>> wrote:
>>>>>>>>
>>>>>>>>
>>>>>>>> On 4/11/18 9:22 AM, MD wrote:
>>>>>>>>
>>>>>>>> Hi Gromacs folks,
>>>>>>>>>
>>>>>>>>> I was trying to use RMSF to compare c-alpha of a wild type and
>>>>>>>>> mutant
>>>>>>>>>
>>>>>>>>>> in a
>>>>>>>>>> 100 ns simulation. I discarded the 10-30 ns and compared them side
>>>>>>>>>> by
>>>>>>>>>> side
>>>>>>>>>> in non-overlapping time windows of 30-40ns, 40-50ns, 50-60ns,
>>>>>>>>>> 60-70
>>>>>>>>>> ns,
>>>>>>>>>> 70-80 ns, 80-90 ns and 90-100ns. The RMSF of wild type and mutant
>>>>>>>>>> overlay
>>>>>>>>>> pretty well with exceptions of some regions with minor flexibility
>>>>>>>>>> differences, but the c-alpha RMSF of wild type went crazy starting
>>>>>>>>>> from
>>>>>>>>>> 70-80ns (7-8 folds of a more drastic change) and lasted until the
>>>>>>>>>> end,
>>>>>>>>>> while the mutant stayed in the same range of changing.
>>>>>>>>>>
>>>>>>>>>> Does this mean that I should trust the simulation after 70ns, or I
>>>>>>>>>> should
>>>>>>>>>> continue the simulation and see if the system will calm down
>>>>>>>>>> eventually?
>>>>>>>>>> Any help will be appreciated.
>>>>>>>>>>
>>>>>>>>>> It sounds to me like one simulation isn't properly corrected for
>>>>>>>>>> PBC
>>>>>>>>>>
>>>>>>>>>> effects (protein jumping back and forth) while the other is. Make
>>>>>>>>>>
>>>>>>>>> sure
>>>>>>>>> the
>>>>>>>>> trajectory is sensible; gmx rmsf doesn't
>>>>>>>>> <https://maps.google.com/?q=trajectory+is+sensible;+gmx+rmsf
>>>>>>>>> +doesn't+&entry=gmail&source=g>intrinsically
>>>>>>>>> account for PBC
>>>>>>>>> so
>>>>>>>>> you have to judiciously apply trjconv before running the analysis.
>>>>>>>>>
>>>>>>>>> -Justin
>>>>>>>>>
>>>>>>>>> --
>>>>>>>>> ==================================================
>>>>>>>>>
>>>>>>>>> Justin A. Lemkul, Ph.D.
>>>>>>>>> Assistant Professor
>>>>>>>>> Virginia Tech Department of Biochemistry
>>>>>>>>>
>>>>>>>>> 303 Engel Hall
>>>>>>>>> 340 West Campus Dr.
>>>>>>>>> Blacksburg, VA 24061
>>>>>>>>>
>>>>>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>>>>>> http://www.thelemkullab.com
>>>>>>>>>
>>>>>>>>> ==================================================
>>>>>>>>>
>>>>>>>>>
>>>>>>>>> --
>>>>>>>>> Gromacs Users mailing list
>>>>>>>>>
>>>>>>>>> * Please search the archive at http://www.gromacs.org/Support
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>>>>>>>>> <https://maps.google.com/?q=/Mailing_Lists/GMX-Users_List+be
>>>>>>>>> fore+pos&entry=gmail&source=g>
>>>>>>>>>
>>>>>>>>> ting!
>>>>>>>>>
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>>>>>>>>>
>>>>>>>>>
>>>>>>>>> --
>>>>>>>>>
>>>>>>>>> ==================================================
>>>>>>>>
>>>>>>> Justin A. Lemkul, Ph.D.
>>>>>>> Assistant Professor
>>>>>>> Virginia Tech Department of Biochemistry
>>>>>>>
>>>>>>> 303 Engel Hall
>>>>>>> 340 West Campus Dr.
>>>>>>> Blacksburg, VA 24061
>>>>>>>
>>>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>>>> http://www.thelemkullab.com
>>>>>>>
>>>>>>> ==================================================
>>>>>>>
>>>>>>> --
>>>>>>> Gromacs Users mailing list
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>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>> --
>>>>>>
>>>>> ==================================================
>>>>>
>>>>> Justin A. Lemkul, Ph.D.
>>>>> Assistant Professor
>>>>> Virginia Tech Department of Biochemistry
>>>>>
>>>>> 303 Engel Hall
>>>>> 340 West Campus Dr.
>>>>> Blacksburg, VA 24061
>>>>>
>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>> http://www.thelemkullab.com
>>>>>
>>>>> ==================================================
>>>>>
>>>>> --
>>>>> Gromacs Users mailing list
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>>>>>
>>>>> --
>>> ==================================================
>>>
>>> Justin A. Lemkul, Ph.D.
>>> Assistant Professor
>>> Virginia Tech Department of Biochemistry
>>>
>>> 303 Engel Hall
>>> 340 West Campus Dr.
>>> Blacksburg, VA 24061
>>>
>>> jalemkul at vt.edu | (540) 231-3129
>>> http://www.thelemkullab.com
>>>
>>> ==================================================
>>>
>>> --
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> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Virginia Tech Department of Biochemistry
>
> 303 Engel Hall
> 340 West Campus Dr.
> Blacksburg, VA 24061
>
> jalemkul at vt.edu | (540) 231-3129
> http://www.thelemkullab.com
>
> ==================================================
>
> --
> Gromacs Users mailing list
>
> * Please search the archive at http://www.gromacs.org/Support
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