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<p class=MsoNormal><span style='font-size:11.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'>Can you run that same procedure without doing anything to your
protein?<o:p></o:p></span></p>
<p class=MsoNormal><span style='font-size:11.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'><o:p> </o:p></span></p>
<p class=MsoNormal><span style='font-size:10.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'>Catch ya,<br>
<br>
Dr. Dallas Warren<br>
</span><span style='font-size:10.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'>Drug Delivery, Disposition and Dynamics</span><span
style='font-size:10.0pt;font-family:"Calibri","sans-serif";color:#1F497D'><br>
</span><span style='font-size:10.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'>Monash Institute of Pharmaceutical Sciences</span><span
style='font-size:10.0pt;font-family:"Calibri","sans-serif";color:#1F497D'>,
Monash University<br>
381 Royal Parade, Parkville VIC 3010<br>
dallas.warren@pharm.monash.edu.au<br>
+61 3 9903 9167<br>
---------------------------------<br>
When the only tool you own is a hammer, every problem begins to resemble a
nail.</span><span style='font-size:11.0pt;font-family:"Calibri","sans-serif";
color:#1F497D'> <o:p></o:p></span></p>
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<p class=MsoNormal><b><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif"'>From:</span></b><span
style='font-size:10.0pt;font-family:"Tahoma","sans-serif"'>
gmx-users-bounces@gromacs.org [mailto:gmx-users-bounces@gromacs.org] <b>On
Behalf Of </b>John Ladasky<br>
<b>Sent:</b> Friday, 19 February 2010 2:08 PM<br>
<b>To:</b> gmx-users@gromacs.org<br>
<b>Subject:</b> [gmx-users] Assembling a good simulation starting point<o:p></o:p></span></p>
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<p class=MsoNormal style='margin-bottom:12.0pt'>Hello everyone,<br>
<br>
I'm a fairly new GROMACS user. I'm running GROMACS 4.0.5 on top of
Ubuntu Linux 9.10. I am still learning a lot.<br>
<br>
I just tried to set up my first fairly complex simulation, and it
failed. I have a protein of interest, a beta barrel with a hydrophobic,
ligand-binding interior. I am interested in making mutations to this
protein, with the goal of getting it to bind to a rather different ligand
than the one it normally binds.<br>
<br>
The way that I propose to go about studying this problem is to construct a
partially-unfolded version of the protein structure, add my ligand of
interest, and then run an energy minimization.<br>
<br>
My first naive attempt to construct the partially-unfolded protein was not
successful. I knew that it might have problems, but I tried it
anyway. Using Biopython, I rotated the atomic coordinates so that the
beta barrel was parallel to an axis. Then I simply pulled all of the
atoms 3 Angstroms away from the axis. Finally, I inserted my ligand.
Visually, inspecting the starting structure with PyMol, I didn't see anything
egregious. However, I could have some unwanted close contacts.<br>
<br>
I got a few "long bond" warnings from pdb2gmx, but I
persisted. I got through genbox, editconf, and my first grompp sucessfully.
But then when I tried the first, position-restrained energy minimization, it
aborted with too many LINCS warnings. I blew the system up.<br>
<br>
These LINCS warnings could come from close contacts, or from large forces in
over-stretched bonds which resulted from my crude approach to expanding the
protein structure. Whatever the cause, I need a smarter way to
start. I am open to ANY suggestions!<br>
<br>
What I THINK I might want to do is to manipulate the starting structure in a
more natural way. For example, selecting some peptide bonds in the beta
turns, and changing their angles. A program which allows me to
manipulate structures, and not just simulate natural forces, is what I think
I need. <br>
<br>
Surely, people who have used GROMACS will have faced problems simliar to
mine. Thanks for your advice!<br>
<br>
John Ladasky<o:p></o:p></p>
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