### Re: [gmx-users] Umbrella Sampling tutorial

```

On 11/10/13 9:14 AM, shahab shariati wrote:

Dear Justin

What you described earlier should not be attempted with "distance"
geometry. It won't work very well. The use of restraints is almost
NEVER necessary, especially in the case where the reference group > is

much more massive than the pulling group.

I want to calculate Potential of mean force as a function of the distance
between the centers of mass of drug and the lipid bilayer.

You said distance geometry won't work very well in my case.

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/05a_pull_tips.html

pull_geometry = position

-Justin

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==

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School of Pharmacy
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University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

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### Re: [gmx-users] Umbrella Sampling tutorial

```

On 11/10/13 5:31 AM, shahab shariati wrote:

Dear Justin

You are right. I should  not extrapolate too literally from your tutorial
to my system.

But, I have a general question:

There is 2 groups in COM pulling method (reference group + pull group).

If I want to use pull_geometry = distance, so, I should fix reference group
to be immobile. Is it true?

What you described earlier should not be attempted with "distance" geometry.  It
won't work very well.  The use of restraints is almost NEVER necessary,
especially in the case where the reference group is much more massive than the
pulling group.

On the other hand, I want to know exactly using position restraining on
reference group is optional or mandatory in COM pulling method?

Almost never used.  More explicitly - you do not need position restraints.

-Justin

--
==

Justin A. Lemkul, Ph.D.
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

jalem...@outerbanks.umaryland.edu | (410) 706-7441

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### Re: [gmx-users] Umbrella Sampling tutorial

```

On 11/9/13 9:38 AM, shahab shariati wrote:

Dear Justin

My system contains lipid bilayer + drug + water molecules.

I want to calculate Potential of mean force as a function of the distance
between the centers of mass of drug and the lipid bilayer.

Box vector along which the pulling is being conducted is Z.

1) Are these issues true about my system?

lipid bilayer = reference group for pulling.
drug molecule = group to which pulling force is applied.

Then, should I use position restraining on the lipid bilayer?

I see no reason for that.  The use of position restraints represents a special
case, the logic for which is described in our paper.  Please do not extrapolate
too literally from my tutorial to your system.

2) The system you considered was the dissociation of a single peptide from
the growing end of an protofibril.

So, in your summary_distances.dat, distance between chain A and chain B was
increased.

But, I want to consider translocation of the drug molecule from water into
the lipid bilayer. On the other hand, I want to consider approaching drug
molecule to lipid bilayer.

So, in my summary_distances.dat, distance between drug molecule and lipid
bilayer will be decrease.

...and then increase, if you want to study the partitioning across the membrane.

My mean is that my case is contrary to your case. Nonetheless, should I use
exactly Pull code section of your md_pull.mdp file?

Absolutely not!  Please refer to the advanced section of the tutorial.  The
settings you will need will be very different from the tutorial, which
represents the simplest possible case of pulling.

-Justin

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==

Justin A. Lemkul, Ph.D.
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

jalem...@outerbanks.umaryland.edu | (410) 706-7441

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### Re: [gmx-users] Umbrella Sampling tutorial

```

On 11/9/13 8:22 AM, shahab shariati wrote:

Daer Justin

I studied your tutorial (Umbrella Sampling). It is very beneficial for me.

The system you considered was the dissociation of a single peptide from the
growing end of an protofibril.

You considered following parameters:

Chain_B: reference group for pulling.
Chain_A: group to which pulling force is applied.
pulling direction was Z.

you placed the center of mass of the protofibril at (3.280, 2.181, 2.4775)
in a box of dimensions 6.560 x 4.362 x 12 by editconf:

editconf -f complex.gro -o newbox.gro -center 3.280 2.181 2.4775 -box 6.560
4.362 12.

I have a question:

You said " pull distance must always be less than one-half the length of
the box vector along which the pulling is being conducted".You pulled a
total distance of 5.0 nm in a 12.0-nm box, to avoid the complications
described above.

Why did you used 2.4775? I think 5.0 is true. Please give me more
explanation. How did you obtained this value?

I knew I needed a rectangular box, given the intrinsic geometry of the protein
complex and the manner in which I was pulling, so I started by building a cubic
box around the pentamer that satisfied normal minimum image convention criteria
based on my cutoffs.  I noted its dimensions and extended the box by 5.0 nm
along z, then added a bit of padding space, because the COM distance itself is
not the only factor that is important; I had to simultaneously account for the
fact that I was unfolding a peptide along the reaction coordinate.  So I added a
bit more space for good measure to avoid spurious PBC interactions at the end of
the reaction coordinate.  It's all fairly empirical, determined stepwise by
accounting for the important features of the system.

-Justin

--
==

Justin A. Lemkul, Ph.D.
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

jalem...@outerbanks.umaryland.edu | (410) 706-7441

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### Re: [gmx-users] umbrella sampling tutorial

```

On 4/29/13 6:42 AM, Shima Arasteh wrote:

Dear Justin,

About Umbrella sampling tutorial, would you please let me know why you created
an index file contains of chain A and chain B?

Also, what's the meaning of 19 and 20 created by a text editoras groups.txt
file? I can not understand this.

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/05_pull.html
again.  It answers both of those questions.

http://www.gromacs.org/Documentation/How-tos/Using_Commands_in_Scripts.

-Justin

--

Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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### Re: [gmx-users] umbrella sampling tutorial quastion

```As I know, it is not necessary to restrain neither reference nor pulled
group. When you apply pulling force, it means you have restrained both of
them.

Dariush

On Mon, Jan 9, 2012 at 4:15 PM, przemek bartha wrote:

> Hello,
> According to Justin's tutorial on umbrella sampling,
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/06_umbrella.html
> could anyone explain, if the molecules are restrained in any way in the
> umbrella sampling part?
> What I mean, is when we pull molecule A from molecule B, we restrain "B"
> to that it does not follow "A" (by adding "pos_res" section in .itp file).
> In my particular case, I pull asparagin asid (ASP) from lisyne (LYS), so I
> have got two .itp files for both molecules. Restraining LYS worked well for
> generating configurations, but failed for umbrella sampling.
> My molecules (including LYS which was restrained) were "flying" randomly
> all over the box which resulted in incorrect PMF courve.
>
> So, during umbrella sampling, shall both the molecules be restrained,
> none, or only one of them? Why?
>
> Przemek
>
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University of Pittsburgh School of Medicine
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USA
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### Re: [gmx-users] umbrella sampling tutorial quastion

```

przemek bartha wrote:

Hello,
According to Justin's tutorial on umbrella sampling,
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/06_umbrella.html
could anyone explain, if the molecules are restrained in any way in the
umbrella sampling part?

The umbrella potential itself is a restraint.

What I mean, is when we pull molecule A from molecule B, we restrain "B"
to that it does not follow "A" (by adding "pos_res" section in .itp file).

The position restraint used during steered MD in the tutorial is different from
the umbrella restraint, practically and conceptually.  Please refer to the
associated paper for the underlying reason.  Position restraints are not
necessarily required for any umbrella sampling process.

In my particular case, I pull asparagin asid (ASP) from lisyne (LYS), so
I have got two .itp files for both molecules. Restraining LYS worked
well for generating configurations, but failed for umbrella sampling.
My molecules (including LYS which was restrained) were "flying" randomly
all over the box which resulted in incorrect PMF courve.

This sounds like more of a problem related to system construction rather than
anything related to restraints, i.e. you have one molecule at the edge of a
periodic boundary.

So, during umbrella sampling, shall both the molecules be restrained,
none, or only one of them? Why?

In principle, no restraint aside from the umbrella potential itself is required
to carry out umbrella sampling.

-Justin

--

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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### Re: [gmx-users] Umbrella Sampling tutorial

```

Steven Neumann wrote:

Hey Gmx Users,

I went through Justin tutorial of umbrella sampling with spacing of 0.2 nm:

Time  COM distance
0  -  0.5
208 -  0.7
218 -  0.92
225 - 1.119
231 - 1.41
235 - 1.61
239 - 1.81
246 - 2.09
253 - 2.3
261 - 2.51
268 - 2.71
276 - 2.91
289 - 3.11
307 - 3.3
325 - 3.5
348 - 3.7
359 - 3.93
371 - 4.1
388 - 4.3
412 - 4.51
423 - 4.7
450 - 4.92
454 - 5

Together 22 windows. I obtained delatG= -37 kcal/mol

Do you have any clue why is that so far away from the value from
tutorial of -50.5 kcal./mol?

Not really.  You don't have the even 0.2-nm spacing that the tutorial calls for,
but I know others have reproduced the value, so it should certainly be possible.

-Justin

--

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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