High-throughput "in silico" screening (e.g. for ligand-protein binding) has been performed on a number of systems. How are such automated simulations performed (I assume they utilize molecular dynamics)?<br><br>
<br><br><br><div class="gmail_quote">On Fri, Jul 31, 2009 at 5:47 PM, Justin A. Lemkul <span dir="ltr"><<a href="mailto:jalemkul@vt.edu">jalemkul@vt.edu</a>></span> wrote:<br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
<div class="im"><br>
<br>
Nancy wrote:<br>
<blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
If it necessary to manually create force field parameters for each molecule, then how can one run a simulation involving a number of arbitrary molecules (e.g. a set of mono and disaccharides) for which there are no existing force fields?<br>
<br>
Do you know of any other MD software package that is capable of running simulations on arbitrary molecules without having to "piece together" a force field for each molecule?<br>
<br>
</blockquote>
<br></div>
Indeed it would be nice if there was a software package that would parameterize your molecule, validate said parameters, then run a meaningful simulation with all the proper conditions. Maybe it could even make coffee...<br>
<br>
All kidding aside, the answer is no. It is the job of the user to generate and validate parameters when none are available. A proper topology is perhaps the most important part of setting up a simulation!<br>
<br>
There are some methods for doing some of this in an automated fashion (i.e., RESP charge derivation, antechamber with GAFF, etc). But the hard truth comes down to one simple fact - if no parameters are already available, you must do that work. It is hard, but necessary. Have a look at the Gromos96 force fields; they contain some monosaccharide building blocks that should give you a reasonable starting point.<br>
<br>
-Justin<br>
<br>
<blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
Thanks,<br>
<br>
Nancy<div><div></div><div class="h5"><br>
<br>
<br>
<br>
<br>
On Fri, Jul 31, 2009 at 4:53 PM, Justin A. Lemkul <<a href="mailto:jalemkul@vt.edu" target="_blank">jalemkul@vt.edu</a> <mailto:<a href="mailto:jalemkul@vt.edu" target="_blank">jalemkul@vt.edu</a>>> wrote:<br>
<br>
<br>
<br>
Nancy wrote:<br>
<br>
Hello,<br>
<br>
I am trying to run a MD simulation on trehalose (glucose<br>
disaccharide) in water. I obtained the PDB file from the URL:<br>
<a href="http://www.rcsb.org/pdb/files/ligand/TRE_model.pdb" target="_blank">http://www.rcsb.org/pdb/files/ligand/TRE_model.pdb</a> . When I run<br>
pdb2gmx on the PDB file:<br>
<br>
pdb2gmx -f TRE_model.pdb -o TRE_model.gro -v<br>
<br>
I chose force field 5 (OPLS) from the list:<br>
<br>
Select the Force Field:<br>
0: GROMOS96 43a1 force field<br>
1: GROMOS96 43a2 force field (improved alkane dihedrals)<br>
2: GROMOS96 45a3 force field (Schuler JCC 2001 22 1205)<br>
3: GROMOS96 53a5 force field (JCC 2004 vol 25 pag 1656)<br>
4: GROMOS96 53a6 force field (JCC 2004 vol 25 pag 1656)<br>
5: OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)<br>
6: [DEPRECATED] Gromacs force field (see manual)<br>
7: [DEPRECATED] Gromacs force field with hydrogens for NMR<br>
8: Encad all-atom force field, using scaled-down vacuum charges<br>
9: Encad all-atom force field, using full solvent charges<br>
<br>
And I received the following error message:<br>
<br>
-------------------------------------------------------<br>
Program pdb2gmx, VERSION 4.0.5<br>
Source code file: pdb2gmx.c, line: 429<br>
<br>
Fatal error:<br>
Atom C1 in residue TRP 1 not found in rtp entry with 24 atoms<br>
while sorting atoms<br>
-------------------------------------------------------<br>
<br>
<br>
Well, pdb2gmx thinks that TRE is tryptophan, so it's looking to<br>
complete a TRP building block. Furthermore, your procedure is<br>
undoubtedly going to fail. Force fields and pdb2gmx are not magic;<br>
they are not equipped to handle any arbitrary molecule you may want<br>
to simulate. None of the force fields provided with Gromacs will<br>
contain information for trehalose by default. There is information<br>
for glucose in some of the force fields (check the .rtp files), and<br>
you may be able to piece trehalose together from that information.<br>
<br>
Otherwise, you will have to go through the *very difficult and<br>
time-consuming* process of parameterization:<br>
<br>
<a href="http://oldwiki.gromacs.org/index.php/Parameterization" target="_blank">http://oldwiki.gromacs.org/index.php/Parameterization</a><br>
<br>
-Justin<br>
<br>
Please help.<br>
<br>
<br>
Thank you,<br>
<br>
Nancy<br>
<br>
<br>
<br>
<br>
<br>
<br>
<br>
------------------------------------------------------------------------<br>
<br>
_______________________________________________<br>
gmx-users mailing list <a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a><br></div></div>
<mailto:<a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a>><div class="im"><br>
<a href="http://lists.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br>
Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a><br>
before posting!<br>
Please don't post (un)subscribe requests to the list. Use the<br>
www interface or send it to <a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a><br></div>
<mailto:<a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a>>.<div class="im"><br>
Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
<br>
<br>
-- ========================================<br>
<br>
Justin A. Lemkul<br>
Ph.D. Candidate<br>
ICTAS Doctoral Scholar<br>
Department of Biochemistry<br>
Virginia Tech<br>
Blacksburg, VA<br></div>
jalemkul[at]<a href="http://vt.edu" target="_blank">vt.edu</a> <<a href="http://vt.edu" target="_blank">http://vt.edu</a>> | (540) 231-9080<div class="im"><br>
<a href="http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin" target="_blank">http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin</a><br>
<br>
========================================<br>
_______________________________________________<br>
gmx-users mailing list <a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a><br></div>
<mailto:<a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a>><div class="im"><br>
<a href="http://lists.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br>
Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before<br>
posting!<br>
Please don't post (un)subscribe requests to the list. Use the www<br>
interface or send it to <a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a><br></div>
<mailto:<a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a>>.<div class="im"><br>
Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
<br>
<br>
<br>
------------------------------------------------------------------------<br>
<br>
_______________________________________________<br>
gmx-users mailing list <a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a><br>
<a href="http://lists.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br>
Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before posting!<br>
Please don't post (un)subscribe requests to the list. Use the www interface or send it to <a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a>.<br>
Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
</div></blockquote><div><div></div><div class="h5">
<br>
-- <br>
========================================<br>
<br>
Justin A. Lemkul<br>
Ph.D. Candidate<br>
ICTAS Doctoral Scholar<br>
Department of Biochemistry<br>
Virginia Tech<br>
Blacksburg, VA<br>
jalemkul[at]<a href="http://vt.edu" target="_blank">vt.edu</a> | (540) 231-9080<br>
<a href="http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin" target="_blank">http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin</a><br>
<br>
========================================<br>
_______________________________________________<br>
gmx-users mailing list <a href="mailto:gmx-users@gromacs.org" target="_blank">gmx-users@gromacs.org</a><br>
<a href="http://lists.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br>
Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before posting!<br>
Please don't post (un)subscribe requests to the list. Use the www interface or send it to <a href="mailto:gmx-users-request@gromacs.org" target="_blank">gmx-users-request@gromacs.org</a>.<br>
Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
</div></div></blockquote></div><br>