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

Wed Apr 11 20:44:33 CEST 2018

On 4/11/18 11:17 AM, MD wrote:
> Hi Justin,
> Another quick question. When we talk about more independent runs, did you
> mean a run with another force field or just simply repeating the run?

Depends on what you're trying to prove. If you want to demonstrate that 
your results are not an artifact of a force field bias, you'd run 
(multiple) simulations with different force fields. Typically, people 
just initiate new simulations with the same force field from different 
starting velocities.

-Justin

> Thanks,
> Ming
>
> On Wed, Apr 11, 2018 at 10:52 AM, MD <refmac5 at gmail.com> wrote:
>
>> Thank you.
>> Ming
>>
>>
>> On Wed, Apr 11, 2018 at 10:46 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>>
>>> On 4/11/18 10:44 AM, MD wrote:
>>>
>>>> Thank you Justin :)
>>>> I wonder what is your strategy when considering what criteria could be
>>>> used
>>>> for determining convergence of the simulation?
>>>>
>>> If all the relevant quantities that I care about are invariant over time
>>> based on error estimates, it's converged.
>>>
>>> -Justin
>>>
>>>
>>> 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 simulatio
>>>>>>>>>>>>>> <https://maps.google.com/?q=is+mean+that+I+should+trust+the+simulatio&entry=gmail&source=g>n
>>>>>>>>>>>>>> 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
>>>>>>>>>>>>>
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>>>>>>>>>>>>> /Mailing_Lists/GMX-Users_List before pos
>>>>>>>>>>>>> <https://maps.google.com/?q=/Mailing_Lists/GMX-Users_List+be
>>>>>>>>>>>>> fore+pos&entry=gmail&source=g>
>>>>>>>>>>>>>
>>>>>>>>>>>>> ting!
>>>>>>>>>>>>>
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>>>>>>>>>>>>> -users
>>>>>>>>>>>>> or
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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
>>>>>>>>>>> /Mailing_Lists/GMX-Users_List before posting!
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>>>>>>>>>>> -users
>>>>>>>>>>> or
>>>>>>>>>>> send a mail to gmx-users-request at gromacs.org.
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>>
>>>>>>>>>>> --
>>>>>>>>>>>
>>>>>>>>>> ==================================================
>>>>>>>>> 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
>>>>>>>>> /Mailing_Lists/GMX-Users_List before posting!
>>>>>>>>>
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>>>>>>>>> or
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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
>>>>>>> /Mailing_Lists/GMX-Users_List before posting!
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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
>>>>> /Mailing_Lists/GMX-Users_List before posting!
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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

==================================================