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On 13/02/2011 5:03 PM, TJ Mustard wrote:
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cite="mid:1174249324.18055.1297577023317.JavaMail.open-xchange@oxusgw01.lxa.perfora.net"
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<p style="margin: 0px;"><span> </span></p>
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On February 12, 2011 at 9:31 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 3:57 PM, TJ
Mustard wrote:
<blockquote type="cite">
<p style="margin: 0px;"><span> </span></p>
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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>
<br>
Mark<br>
<blockquote
cite="mid:1174249324.18055.1297577023317.JavaMail.open-xchange@oxusgw01.lxa.perfora.net"
type="cite">
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<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>
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<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>
</div>
<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 class="moz-txt-link-abbreviated" href="mailto:mustardt@onid.orst.edu">mustardt@onid.orst.edu</a></p>
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