<html><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; "><br><div><div>On Feb 23, 2011, at 3:21 AM, Jianguo Li wrote:</div><br class="Apple-interchange-newline"><blockquote type="cite"><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font-family: 'times new roman', 'new york', times, serif; font-size: 12pt; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br>Thank you for the the useful information, XAvier.<br>My peptide is highly positively charged, 18 AA with +12 charges. Other of my group members told me their NMR experiment in water indicates the peptide conformation is very dynamics. Actually I also did peptide refolding using REMD in water, and I found it is flexible and has no stable structure in water, except some instantaneously helical structures. In addition, my peptide consists of two branches connected by unnatural peptide bond, so the backbone is discontinuous, and also because of the high charges, I assume the peptide doesn't form helcial structure in the negatively charged membrane. Therefore I didn't put any constraints in the peptide to keep the secondary structure of the peptide. I know there are assumptions in my model, but I have no other information to increase the accuracy of the model. In fact, when I am doing REMD folding simulations using Gromos53a6 and CHARMM27 with cMap, I got different results. But the common thing is that both results seems to indicate the peptide is filexbile in water without stable secondary structure. Then I used MARTINI FF with flexible structure, just to find some general features.<br><br>I will try your suggestion, doing REMD in those bad windows.<br> <br>And the reference you mentioned is very useful, I will take a look at them :-)<br><br>Another question: Suppose some other tools support using different temperatures in different windows, as you mentioned, if 500K is too high to have a significant contribution to the probability of 300K, can I do a series of simulation in a certain window with different temparatures (e.g. 300K, 350K, 400K,450K, 500K). In such cases, in each window, I need to do 5 simulations, which will be much cheaper than doing REMD in that window.<span class="Apple-converted-space"> </span></div></div></div></span></blockquote>It would be computationally cheaper but this is assuming that you'd get the info you are looking for within these simulations and again the weight of the conformations from 400/450/500 K at 300 K is questionable. Note also that the conformations sampled at high temperature with position restrains on the lipids to avoid deformation will be difficult to interpret! </div><div><blockquote type="cite"><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; font-size: medium; "><div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font-family: 'times new roman', 'new york', times, serif; font-size: 12pt; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br>Cheers<br>Jianguo<br><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font-family: 'times new roman', 'new york', times, serif; font-size: 12pt; "><br><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font-family: 'times new roman', 'new york', times, serif; font-size: 12pt; "><font size="2" face="Tahoma"><hr size="1"><b><span style="font-weight: bold; ">From:</span></b><span class="Apple-converted-space"> </span>XAvier Periole <<a href="mailto:x.periole@rug.nl">x.periole@rug.nl</a>><br><b><span style="font-weight: bold; ">To:</span></b><span class="Apple-converted-space"> </span>Discussion list for GROMACS users <<a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a>><br><b><span style="font-weight: bold; ">Sent:</span></b><span class="Apple-converted-space"> </span>Tuesday, 22 February 2011 21:18:12<br><b><span style="font-weight: bold; ">Subject:</span></b><span class="Apple-converted-space"> </span>Re: [gmx-users] Can g_wham support using different temperature for different windows?<br></font><br><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">A few notes:</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">- the original method (Kumar-JCC-1992) that inspired wham was actually </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">developed to mix different temperature simulations. It is however not clear </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">for the type of system you are simulating how much a 500K simulation </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">would be useful to improve the sampling at 300 K or so. The reason is </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">that the enthalpy difference between the two systems is so high that the </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">probability that a conformation from a 500K simulation would contribute</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">to sampling at 300K is really low. It would much more efficient for systems </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">with implicit solvent for which the energy of the system does not vary so </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">much with the temperature. One could look at Chodera-JCTC-2007 </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">and ref therein for a few examples.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">- I would think that a REMD simulation would be more useful. No need to</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">run 30 replicas to very hight temperature! A bilayer at 500K might get funny.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">- Martini force field for flexible regions of protein should not be trusted ... or</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">really interpreted with a lot of reserve. The "coil" definition is simply something</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">flexible with absolutely no guaranty that it could be representing some thing </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">even close to reality, which we have only an approximate idea of what it is! </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">- A peptide in a bilayer has a very high chance to get into a helical conformation.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Do you think it is reasonable to keep it "flexible"? </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">- As noted by Justin and Chris, you definitely have a problem of convergence ... </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">I am not sure how many "converged" examples of PMFs of peptide crossing a</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">bilayer are out in the literature (Justin?) but from our experience with Martini </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">it does take an awful lot of time to really get convergence. For you system I </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">would expect at least a microsecond for the windows where sampling is an </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">issue. As an example, we saw significant differences on a PMF between two </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">simple helices up to 8 us ... and no charges were involved.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">This might be a lot pessimistic but you should not get fooled by a CG model.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Martini is really good for a lot of things but other things should really but be</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">looked at carefully. </div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">XAvier.</div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">On Feb 22, 2011, at 9:12 AM, Jianguo Li wrote:</div><br class="Apple-interchange-newline"><blockquote type="cite"><span class="Apple-style-span" style="border-collapse: separate; color: rgb(0, 0, 0); font-family: Helvetica; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; font-size: medium; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font-family: times, serif; font-size: 12pt; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Sorry I forgot to attach my mdp files. <br><br>Here is the mdp file for pulling simulaition:<br>-------------------------------------------------------------------------<br></div></div></div></span></blockquote></div><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><div style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><br></div></div></div></div></div><br>--<span class="Apple-converted-space"> </span><br>gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br><a href="http://lists.gromacs.org/mailman/listinfo/gmx-users">http://lists.gromacs.org/mailman/listinfo/gmx-users</a><br>Please search the archive at<span class="Apple-converted-space"> </span><a href="http://www.gromacs.org/Support/Mailing_Lists/Search">http://www.gromacs.org/Support/Mailing_Lists/Search</a><span class="Apple-converted-space"> </span>before posting!<br>Please don't post (un)subscribe requests to the list. Use the<span class="Apple-converted-space"> </span><br>www interface or send it to<span class="Apple-converted-space"> </span><a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>.<br>Can't post? Read<span class="Apple-converted-space"> </span><a href="http://www.gromacs.org/Support/Mailing_Lists">http://www.gromacs.org/Support/Mailing_Lists</a></div></span></blockquote></div><br></body></html>