[gmx-users] Justin paper 2010 pulling

Justin Lemkul jalemkul at vt.edu
Mon Sep 17 14:30:44 CEST 2018

```
On 9/17/18 8:25 AM, Rakesh Mishra wrote:
> Agreed with this
>
> "Newtonian mechanics always apply, but it's not as simple as "pull on X,
> and Y moves." Your system evolves under the influence of the biasing force."

Perhaps my nomenclature was bad here - X and Y are not Cartesian
directions, they are the groups that you're specifying in the .mdp file
that define the vector of the pulling force.

> The same I am saying that on  Pulling X, X will fell equal and opposite but
> not Y and  Z.

Correct.

> Meaning ,
> If 3' of one strand will Pull  along X then 3' (reference group , which is
> not fixed )of complimentary strand  will move opposite along X . while Y
> and  Z
> those where no biasing force are applied, so Y and Z are  free to move in
> random (any direction ).
>
>
> Simple representation form your tutorial like.
> In my thinking in this following protocol r_24 and r_12 will move
> oppositely along X direction. But not Y and Z.

The problem here is the the groups *will not* necessarily "move
oppositely along X." Your biasing force causes a net increase in the
length of the vector connecting r_12 and r_24. That's it. Perhaps that
means one group moves and the other oscillates in place. Maybe they do,
in fact, move in different directions. The net motion of any group
depends on all of the forces in the system. Maybe your biasing potential
causes a local helical unwinding, allowing water to enter in between the
bases or the hydrogen bonding structure changes, which then causes
different diffusion in any dimension. But the biasing force only ever
applies along X.

-Justin

> pull_ngroups               = 2
> pull_ncoords               = 1
> pull_group1_name        = r_24         ; 3' of  chain B of dsDNA as a
> reference gorup (not  fixed)
> pull_group2_name        = r_12          ;  3' of  chain A of dsDNA as a
> pulling gorup
> pull_coord1_type          = umbrella      ; harmonic biasing force
> pull_coord1_geometry   = distance      ; simple distance increase
> pull_coord1_groups       = 1  2
> pull_coord1_dim           = Y  N  N
> pull_coord1_rate          = 0.005          ; 0.005 nm per ps = 5nm per 1 ns
> pull_coord1_k              = 1000          ; kJ mol^-1 nm^-2
> pull_coord1_start         = yes           ; define initial COM distance > 0
>
>
>
>
> On Mon, Sep 17, 2018 at 5:18 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 9/17/18 4:52 AM, Rakesh Mishra wrote:
>>
>>> Agreed.
>>>
>>> But, I could not solve.
>>>    So Justin, If I pull 3' end of one strand of DNA by taking as
>>> 3' end of the complimentary strand as a reference group (Note that
>>> I have not fixed or not made it immobile ) then according to the theory of
>>> newtons third law reference group (which is not immobile or not fixed )
>>> will get
>>> same equal and opposite pull and will move in the opposite direction.
>>> am I correct.
>>>
>> You set two groups that define a vector along which a biasing potential is
>> applied. The net displacement of either of those groups (or any other atoms
>> in the system) is a function of the total force acting on all of the atoms.
>> Newtonian mechanics always apply, but it's not as simple as "pull on X, and
>> Y moves." Your system evolves under the influence of the biasing force.
>>
>> Your results are probably somewhat confounded by the fact that you're
>> pulling along a vector that is oblique to both the helical axis and the
>> hydrogen-bonding plane. It's not trivial to apply forces to duplex DNA, so
>> judicious choice of pulling vector is critical.
>>
>> -Justin
>>
>>
>>
>>> On Fri, Sep 14, 2018 at 5:11 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>> On 9/14/18 3:14 AM, Rakesh Mishra wrote:
>>>>
>>>> Dear Dr. Justin,
>>>>> Of course I agree with your points. There is no point to not believe on
>>>>> you,
>>>>> that's why we are discussing and thanks for your comment.
>>>>> I raised the question because I observed the problem .
>>>>> And it was matter of just common sense for me that
>>>>> why the change of saving frequency is affecting the much difference
>>>>> in the maximum value of force curve in pulling along the axial
>>>>> direction.
>>>>>
>>>>> Let me clear again, I say Input parameters of the pull.mdp files are
>>>>> same
>>>>> for both the simulation.
>>>>> Only difference is the different saving frequency of position and energy
>>>>> coordinates.
>>>>> Please see below two cases
>>>>>
>>>>> Case -A
>>>>>
>>>>>      simulation of same system with same input parameter during pulling
>>>>> 1  nstxtcout    = 2000       ; every 4 ps
>>>>>        nstenergy    = 5000
>>>>>
>>>>> 2  nstxtcout    = 2000       ; every 4 ps
>>>>>        nstenergy    = 2000
>>>>>
>>>>>       (output files, pullf1.xvg, and pullf2.xvg are different very much
>>>>> w.r.t
>>>>> peak value of force )
>>>>>        Same thing happening also in the following below case, please see
>>>>> this.
>>>>>
>>>>> Case B.
>>>>>
>>>>> 1  nstxtcout    = 2000       ; every 4 ps
>>>>>        nstenergy   = 5000
>>>>>
>>>>> 2-  nstxtcout    = 1000       ; every 4 ps
>>>>>         nstenergy   = 5000
>>>>>
>>>>> Because, now this gromacs discussion user platform do not allow to
>>>>> any other data (eg, plot, pdf file etc) otherwise I can upload the plot.
>>>>>
>>>>> You can always upload images to file-sharing services and provide links.
>>>> But first, watch the trajectories and see how they're behaving. The
>>>> systems are likely just doing somewhat different things, as I said
>>>> before.
>>>> There is no reason to expect even the exact same .tpr file to produce the
>>>> exact same output (binary identical), for reasons stated here:
>>>> http://www.gromacs.org/Documentation/Terminology/Reproducibility
>>>>
>>>> Again, I emphasize that output control has no impact on the computation
>>>> of
>>>> forces or anything to do with the pull code. This cannot be the reason
>>>> for
>>>> differences in trajectories.
>>>>
>>>> -Justin
>>>>
>>>> On Thu, Sep 13, 2018 at 4:57 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>>
>>>>> On 9/13/18 1:20 AM, Rakesh Mishra wrote:
>>>>>> I do not believe .
>>>>>>
>>>>>>> Because if I run multiple simulation of pulling with the same system
>>>>>>> and
>>>>>>> with the
>>>>>>> same inputs then almost we are getting similar force/time curve.
>>>>>>> While we are getting different curve if we are saving position
>>>>>>> coordinates
>>>>>>> or energy
>>>>>>> coordinates with different frequency.
>>>>>>>
>>>>>>> There is no aspect of the code in which the computation of forces
>>>>>>>
>>>>>> depends
>>>>>> on output frequency. You're welcome to disbelieve me, but you're
>>>>>> clearly
>>>>>> just getting different simulation outcomes from different inputs, or
>>>>>> there's something else that differs that you haven't realized or
>>>>>> haven't
>>>>>> told us.
>>>>>>
>>>>>> -Justin
>>>>>>
>>>>>>
>>>>>> On Wed, Sep 12, 2018 at 8:15 PM, Justin Lemkul <jalemkul at vt.edu>
>>>>>> wrote:
>>>>>>
>>>>>> On 9/12/18 8:42 AM, Rakesh Mishra wrote:
>>>>>>>> Dear Justin
>>>>>>>>
>>>>>>>> It is totally surprised for me.
>>>>>>>>>       I am pulling the same system of bdna
>>>>>>>>> with the same constant velocity (0.005nm/ps).
>>>>>>>>>
>>>>>>>>> Case 1
>>>>>>>>> let for first case, When I am saving position coordinate (nstxtc )
>>>>>>>>> in
>>>>>>>>> the
>>>>>>>>> interval of 4ps
>>>>>>>>> and saving energy coordinate in the interval of 4ps.
>>>>>>>>>
>>>>>>>>> Case 2
>>>>>>>>> In the second case of pulling of the same system with the same
>>>>>>>>> velocity,
>>>>>>>>> we
>>>>>>>>> save position
>>>>>>>>> coordinate in the interval of 4ps but we save energy coordinate in
>>>>>>>>> the
>>>>>>>>> interval of  10ps.
>>>>>>>>>
>>>>>>>>> Now in the output file of force.xvg for both case qualitative
>>>>>>>>> behaviour
>>>>>>>>> of
>>>>>>>>> diagram is same but
>>>>>>>>> Peak of the forces are much differ.  Why this saving frequency is
>>>>>>>>> affecting
>>>>>>>>> the peak value. While
>>>>>>>>> it is just saving the coordinates.
>>>>>>>>>
>>>>>>>>> We also found that, if we save energy coordinate with the same
>>>>>>>>> frequency
>>>>>>>>> and position
>>>>>>>>> coordinate with different frequency then, again peak value of forces
>>>>>>>>> are
>>>>>>>>> different.
>>>>>>>>> Which should not. Why it is happening. Can you clarify please.
>>>>>>>>>
>>>>>>>>> Your results have nothing to do with the save frequency. The output
>>>>>>>>> in
>>>>>>>>>
>>>>>>>>> pullf.xvg is specified by pull-nstfout, not any of the others. You
>>>>>>>> have
>>>>>>>> different simulations that behave differently, because there are
>>>>>>>> elements
>>>>>>>> of randomness in any MD simulation. Pulling is a non-equilibrium
>>>>>>>> process;
>>>>>>>> you may have to run several times with different pull vectors to find
>>>>>>>> the
>>>>>>>> minimum-energy path.
>>>>>>>>
>>>>>>>> -Justin
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>> On Thu, Sep 6, 2018 at 5:20 PM, Justin Lemkul <jalemkul at vt.edu>
>>>>>>>> wrote:
>>>>>>>>
>>>>>>>> On 9/6/18 2:29 AM, Rakesh Mishra wrote:
>>>>>>>>> While I have purely physics background.
>>>>>>>>>> But, In my thinking, there are hydrogen bonds (electrostatic
>>>>>>>>>>
>>>>>>>>>>> attractive
>>>>>>>>>>> interaction)
>>>>>>>>>>> between bp of  both the strands of DNA/RNA  which are
>>>>>>>>>>> perpendicular
>>>>>>>>>>> to
>>>>>>>>>>> helix direction.
>>>>>>>>>>> And the other thing you have chosen very fast velocity like (0.01,
>>>>>>>>>>> 0.001,
>>>>>>>>>>> 0.005 ).
>>>>>>>>>>> This can also be the reason of smoothness. But can you tell me one
>>>>>>>>>>> thing
>>>>>>>>>>> value of spring constant of biasing that you have taken (k= 1000),
>>>>>>>>>>> is
>>>>>>>>>>> standard or not . If this value can be taken for peptide pulling .
>>>>>>>>>>> Can
>>>>>>>>>>> this value of
>>>>>>>>>>> spring constant (k=1000) can be taken  for DNA (or dna+drug)
>>>>>>>>>>> pulling
>>>>>>>>>>> or
>>>>>>>>>>> not .
>>>>>>>>>>>
>>>>>>>>>>> There is no such thing as a "standard" force cons
>>>>>>>>>>> 22+force+cons&entry=gmail&source=g>tant
>>>>>>>>>>> for pulling.
>>>>>>>>>>>
>>>>>>>>>>> -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
>>>>>>>>>>
>>>>>>>>>> ==================================================
>>>>>>>>>>
>>>>>>>>>> --
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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
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>>>>>> * Please search the archive at http://www.gromacs.org/Support
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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
>> /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

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

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