Hi Tom,<br><br>1 ns sounds far too small to explore the various conformational states of a protein of that size, and even worse if you expect the ligand to find it lowest-energy conformation/position (unless you have placed it where it binds). Perhaps you should consider enhanced sampling techniques like metadynamics, accelerated MD, the adaptive biasing force method, conformational flooding, hyperdynamics, etc. There is a plugin for GROMACS (works for other MD engines as well) to perform metadynamics variations named "PLUMED". At their website (<font size="3"><span style="line-height: 19px;"><a href="http://www.plumed-code.org">www.plumed-code.org</a>) </span></font>you can find many papers about metadynamics, but here are a few ones to start from:<br>
<br>G. Bussi, F. L. Gervasio, A. Laio, M. Parrinello, "Free-energy landscape for beta hairpin folding from combined parallel tempering and metadynamics", J. Am. Chem. Soc. 128 (41) (2006) 13435–41.<br><br>] C. Camilloni, D. Provasi, G. Tiana, R. A. Broglia, "Exploring the protein G helix free-energy surface by solute tempering metadynamics", Proteins 71 (2008) 1647.<br>
<br>S. Piana, A. Laio, "A bias-exchange approach to protein folding", J. Phys. Chem. B 111 (17) (2007) 4553–9.<br><br><br>To get a flavor about the time scales that a ligand needs to find its lowest-energy conformation/pocket with unguided MD simulations, have a look at this recent letter:<br>
<br><div class="auths"><font size="2">J Am Chem Soc. 2011 Jun 22;133(24):9181-3. Epub 2011 May 13.</font><font size="2"> "How does a drug molecule find its target binding site?", Shan Y, Kim ET, Eastwood MP, Dror RO, Seeliger MA, Shaw DE.</font></div>
<br><br>hope this helps,<br>Thomas<br><br><br><br><div class="gmail_quote">On 27 July 2011 02:23, Tom Dupree <span dir="ltr"><<a href="mailto:t.dupree@unsw.edu.au">t.dupree@unsw.edu.au</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin: 0pt 0pt 0pt 0.8ex; border-left: 1px solid rgb(204, 204, 204); padding-left: 1ex;">
Greetings all,<br>
I am quite interested in this discussion, and wondered if some people would like to add how they would assess the length their MD simulations. I am currently simulating HIV-1 RT for 1 ns and seem to have very flat energy profiles for almost anything (energy wise) I care to measure and yet ligand position/conformation continues to change throughout the simulation.<br>
<br>
Tom<br>
<br>
Widya Desmarani wrote:<br>
> Dear gromacs user,<br>
><br>
> I have been trying to look for an answer for my following question from<br>
> our forum but still couldn't manage to find one. Probably it is trivial<br>
> but I am not sure.<br>
><br>
> Instead of running a single relatively long simulation (say for about 30<br>
> ns), is it acceptable if we simulate multiple short simulations (say 15<br>
> simulations where each of them is 2 ns), and then, all the resulted<br>
> trajectories are merged/concatenated into one single trajectory with the<br>
> amount of total simulation 30 ns? I am interested in investigating bulk<br>
> properties of liquid, such as compressibility, diffusion, and dielectric.<br>
><br>
<br>
There is no need to concatenate the trajectories, and moreover it may give you a<br>
misleading result. Every simulation needs time to equilibrate. In the limit of<br>
infinite sampling, all simulations should converge to the same properties, on<br>
average. Whether or not your simulation can produce stable properties in 2 ns<br>
is something you'll have to decide. If 2 ns is insufficient, then you're still<br>
not collecting data that are as reliable as you would get from a longer<br>
simulation.<br>
<br>
Multiple simulations from independent starting velocities and/or configurations<br>
are generally expected. A single simulation does not necessarily tell you the<br>
whole truth.<br>
<br>
-Justin<br>
<br>
--<br>
========================================<br>
<br>
Justin A. Lemkul<br>
Ph.D. Candidate<br>
ICTAS Doctoral Scholar<br>
MILES-IGERT Trainee<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>
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<p style="margin-bottom: 0cm;" align="LEFT">======================================================================</p>
<p style="margin-bottom: 0cm;" align="LEFT">Thomas Evangelidis</p>
<p style="margin-bottom: 0cm;" align="LEFT">PhD student</p>
<p style="margin-bottom: 0cm;" align="LEFT">Biomedical Research
Foundation, Academy of Athens</p>
<p style="margin-bottom: 0cm;" align="LEFT">4 Soranou Ephessiou , 115 27
Athens, Greece<br><br>email: <a href="mailto:tevang@bioacademy.gr" target="_blank">tevang@bioacademy.gr</a></p>
<p style="margin-bottom: 0cm;" align="LEFT"> <a href="mailto:tevang3@gmail.com" target="_blank">tevang3@gmail.com</a></p>
<p style="margin-bottom: 0cm;" align="LEFT"><br>website:
<a href="https://sites.google.com/site/thomasevangelidishomepage/" target="_blank">https://sites.google.com/site/thomasevangelidishomepage/</a></p>
<p style="margin-bottom: 0cm;" align="LEFT"><br>
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<br>