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On 13/02/2011 6:07 PM, TJ Mustard wrote:
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cite="mid:1461181012.18089.1297580867657.JavaMail.open-xchange@oxusgw01.lxa.perfora.net"
type="cite">
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<p style="margin: 0px;"><span> </span></p>
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On February 12, 2011 at 10:14 PM Mark Abraham
<a class="moz-txt-link-rfc2396E" href="mailto:Mark.Abraham@anu.edu.au"><Mark.Abraham@anu.edu.au></a> wrote:<br>
<br>
<blockquote type="cite" style="margin-left: 0px; padding-left:
10px; border-left: 1px solid blue;"> On 13/02/2011 5:03 PM, TJ
Mustard wrote:
<blockquote type="cite">
<p style="margin: 0px;"><span> </span></p>
<div style="margin: 5px 0px;"> <br>
On February 12, 2011 at 9:31 PM Mark Abraham <a
moz-do-not-send="true"
href="mailto:Mark.Abraham@anu.edu.au"><Mark.Abraham@anu.edu.au></a>
wrote:<br>
<br>
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;"> On
13/02/2011 3:57 PM, TJ Mustard wrote:
<blockquote type="cite">
<p style="margin: 0px;"><span> </span></p>
<div style="margin: 5px 0px;"> <br>
On February 12, 2011 at 5:35 PM Mark Abraham <a
moz-do-not-send="true"
href="mailto:Mark.Abraham@anu.edu.au"><Mark.Abraham@anu.edu.au></a>
wrote:<br>
<br>
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;">
On 13/02/2011 11:49 AM, TJ Mustard wrote:
<blockquote type="cite">
<p style="margin: 0px;">Hi all,</p>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">I have been testing the
ability of taking a sphere of a protein around
a ligand, and positionally restrain the
specified alpha carbons. I was hoping to keep
non connected protein chains from drifting
apart. I have been able to run these md/fep
jobs, but I get huge interaction energies for
the ligand, which has no positional restraints
on it. I also don't restrain any atoms within
the rvdw, rcoulomb and rlist radii. Am I
thinking this is a possibility when it is
physically impossible to simulate?</p>
</blockquote>
<br>
I doubt it.<br>
<br>
<blockquote type="cite">
<p style="margin: 0px;">Currently I am selecting
all residues around the ligand that have an
atom within 20 Angstroms. I then save this as
a pdb file and then run it through pdb2gmx,
manually create a posres.itp file for each
"chain" with their first and last residue's
alpha carbon. Once I turn off these positional
restraints the FEP energies drop down to
"normal" levels.</p>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">Does anyone have an idea
what is happening?</p>
<br>
And if you do, can you please give a
recommendation?<br>
</blockquote>
<br>
I'd guess you're not restraining how you think you
are :-) Bear in mind that position restraints are
indexed relative to a [moleculetype] (and must be
#included there), and not the whole system. </blockquote>
</div>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">First I tried setting this
globally it the .top file with the numbering
corresponding to the atoms in question there, but
found that the .top file only runs the solvent
molecules and all of my reference atoms were outside
the parameters (atoms 1-3 for water).</p>
</blockquote>
<br>
By default -DPOSRES will only restrain solvent because
a) that's all it's meant to do, because b) that
[position_restraints] block is local to the SOL
[moleculetype], like I said.<br>
<br>
<blockquote type="cite">
<p style="margin: 0px;">Then I setup the restraints
argument in the Protein_chain_A.itp.itp file to
reference the posre_Protein_ends_chain_A.itp file I
made.</p>
<br>
; Include Position restraint file<br>
#ifdef POSRES_PROTEIN<br>
#include "posre_Protein_ends_chain_A.itp"<br>
#endif<br>
<br>
<p style="margin: 0px;">In the
posre_Protein_ends_chain_A.itp file I entered the
alpha-C atoms (2 total both the first residue and
last) for the protein.</p>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">[ position_restraints ]<br>
; atom type fx fy fz<br>
5 1 1000 1000 1000<br>
262 1 1000 1000 1000</p>
</blockquote>
<br>
Well, that should work, if you put this in the right
[moleculetype] block. Whether that's enough of a
restraint can't be said.<br>
</blockquote>
</div>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">Well my major problem is the energy
being transmitted about 12 angstroms away into my FEP
molecule. I have consistently gotten an interaction energy
of around ~130 kJ/mol. With these restraints on the energy
spikes to ~125000 kJ/mol. Since I have my rvdw, rcoulomb,
rlist being 1.0 (nm), do I need to move these constraints
father away from the ligand?</p>
</blockquote>
<br>
Hence my thinking that you're somehow applying restraints to
the wrong [moleculetype] and the FEP is amplifying the
problem. Can you run normal MD normally, with and without
restraints?<br>
</blockquote>
</div>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">I have ran these jobs without the
restraints, and the FEP energy is ~130kJ/mol. I can run the md
(actually in sd) but I am not sure what you mean.</p>
</blockquote>
<br>
When trouble-shooting, eliminating sources of problems is critical.
If you can run a non-FEP simulation with your position restraints,
then they are probably not the source of the problem. If FEP without
restraints works, and non-FEP with restraints works, and FEP with
restraints doesn't, then someone can work out what to try next.
Until then, the simplest hypothesis is that your restraints don't
work (either by design or implementation flaws). :-)<br>
<br>
Mark<br>
<blockquote
cite="mid:1461181012.18089.1297580867657.JavaMail.open-xchange@oxusgw01.lxa.perfora.net"
type="cite">
<p style="margin: 0px;">Thank you,</p>
<p style="margin: 0px;">TJ Mustard</p>
<p style="margin: 0px;"> </p>
<div style="margin: 5px 0px;">
<blockquote type="cite" style="margin-left: 0px; padding-left:
10px; border-left: 1px solid blue;"> Mark<br>
<blockquote type="cite">
<div style="margin: 5px 0px;">
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;">
<blockquote type="cite"> <br>
<div style="margin: 5px 0px;">
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;">
The combination of g_select and genrestr is
probably a more reliable and documentable way to
generate your position restraints.<br>
</blockquote>
</div>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">I tried using genrestr
directly and found that the selection was limited to
the presets. I then tried to run a make_ndx to
select the residues that were the starting and
terminating ends, but I don't know how and if this
program can do this task. I could manually find the
residue numbers and input them directly but knowing
that I was looking to restrain 6 atoms I decided to
do it manually.</p>
</blockquote>
<br>
I thought you were trying to get all the alpha carbons
outside a sphere, sorry. For just 6 atoms, sure do it by
hand.<br>
<blockquote type="cite">
<p style="margin: 0px;">I have yet to look at
g_select, as I am just seeing if this idea would
work before I start making a automated script for
this.</p>
</blockquote>
<br>
The point here is that it is straightforward to use
g_select to "make an index group of alpha carbons
further than a given distance from some location" and
now you can use genrestr to make position restraints for
that whole group.<br>
</blockquote>
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<p style="margin: 0px;"> </p>
<p style="margin: 0px;">I have just looked into this and I
will hopefully be able to use this for the other projects
I have.</p>
<p style="margin: 0px;"> </p>
<div style="margin: 5px 0px;">
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;">
<blockquote type="cite">
<p style="margin: 0px;">Would there be a better way to
hold these atoms in the respective locations. I
could hold there distances constant.</p>
</blockquote>
<br>
Also possible, but (IIRC) the atoms have to be part of
the same [moleculetype], which is awkward for
inter-chain restraints. Either way, you have to address
whether your restraints are perturbing the dynamics.<br>
</blockquote>
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<p style="margin: 0px;"> </p>
<p style="margin: 0px;">Well I will stay away from this for
now then.</p>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;">Thank you,</p>
<p style="margin: 0px;">TJ Mustard</p>
<p style="margin: 0px;"> </p>
<div style="margin: 5px 0px;">
<blockquote type="cite" style="margin-left: 0px;
padding-left: 10px; border-left: 1px solid blue;"> Mark<br>
</blockquote>
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<p style="margin: 0px;"> </p>
<p style="margin: 0px;"> </p>
<p style="margin: 0px;"> </p>
<p style="font-family: monospace; white-space: nowrap;
margin: 5px 0px;">TJ Mustard<br>
Email: <a moz-do-not-send="true"
href="mailto:mustardt@onid.orst.edu">mustardt@onid.orst.edu</a></p>
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<br>
</blockquote>
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<p style="margin: 0px;"> </p>
<p style="font-family: monospace; white-space: nowrap; margin: 5px
0px;">TJ Mustard<br>
Email: <a class="moz-txt-link-abbreviated" href="mailto:mustardt@onid.orst.edu">mustardt@onid.orst.edu</a></p>
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