Sorry to be slow to chime in here, but there are several reasons one might run into hysteresis, even when not using "slow growth":
1) The aforementioned bug 2) Topology errors 3) Convergence problems. Of 3), there could be many different types. A recurring source of these problems is when people fail to use soft core potentials when inserting/deleting atoms, or simply use wacky soft core parameters. Or when they leave on electrostatic interactions on atoms that are being removed using soft core. etc. Some discussion of these common issues is at http://www.alchemistry.org and there are lots of relevant references in the literature. There are various other explanations for hysteresis too (though most fall into subcategories of 3). I could imagine these might be a big deal when doing something like changing chirality. Basically if you are doing something where there is a conformational change (like in chirality) there will be some intermediate region of your control parameter where, to converge, the "system" (whatever that is) will need to switch back and forth between conformations in order to converge. Often, correlation times will be very long here and it can be very hard to achieve convergence, hence you'll see hysteresis. You should obviously invest more computational effort in this intermediate region than everywhere else to try and blast through the sampling problem -- or use an enhanced or biased sampling scheme that can help. David On Mon, Jun 16, 2008 at 12:01 PM, Justin A. Lemkul <[EMAIL PROTECTED]> wrote: > The bug report can be found here: > > http://bugzilla.gromacs.org/show_bug.cgi?id=175 > > The thread that gave rise to this report starts here: > > http://www.gromacs.org/pipermail/gmx-users/2007-November/030534.html > > -Justin > > Diana Lousa wrote: >> >> Hello, >> >> I'm having a similar problem, i.e. inconsistency between forward and >> reverse free energy calculations, in changing the chirality of a dihedral. >> In my case it is unlikely that there is histeresis, given that I have a >> long simulation. Could you be more specific about the bug you're referring >> to, I checked the reported known bugs and didn't find anything that was >> likely to cause this strange results. >> >> Thanks >> >> Diana Lousa >> Instituto de Tecnologia Química e Biológica >> Universidade Nova de Lisboa >> Av. da República – EAN, >> 2780-157 Oeiras >> PORTUGAL >> >> >> ---------- Forwarded message ---------- >> From: Justin A. Lemkul <[EMAIL PROTECTED] <mailto:[EMAIL PROTECTED]>> >> Date: 2008/6/16 >> Subject: Re: [gmx-users] Re: forward and reverse free energy not >> consistant (Li Qiang) >> To: Discussion list for GROMACS users <gmx-users@gromacs.org >> <mailto:gmx-users@gromacs.org>> >> >> >> Which GMX version are you using? There's a known bug in version 3.3.1 >> that has been fixed in 3.3.3. <http://3.3.3.> >> >> -Justin >> >> friendli wrote: >> > >> > Hi, >> > >> > I use thermodynamics integration. The protocol is 1000step energy >> > minimization, 20 ps bond-constraint MD, and then 200ps MD for collecting >> > dgdl. >> > >> > thanks >> > >> > Qiang >> > >> > Gerrit Groenhof wrote: >> >> >> >> Looks like hysteresis. Do you do slow growth, or discrete FEP? >> >> >> >> Gerrit >> >> >> >> >> >> >> >>> Dear all Gmxers, >> >>> >> >>> I am calculating a mutation free energy from L<->A for a five AA >> >>> peptides using G96 53a6 force field. >> >>> however, my dG_for and dG_rev is quite different. >> >>> dG_for(lambda=0.00) = - 9.9 kJ/mol >> >>> dG_rev(lambda=1.00) = 1.33 kJ/mol >> >>> >> >>> Is there anything wrong with setting up topologies? >> >>> >> >>> Here is the [atoms] part for morphed atoms. and I attached the full >> >>> .top in the attachment. >> >>> For L->A: >> >>> [ atoms ] >> >>> 17 CH2 2 LEU CB 6 0 14.027 >> >>> CH3 0 15.035; qtot 1 >> >>> 18 CH1 2 LEU CG 7 0 13.019 >> >>> DUM 0 13.019; qtot 1 >> >>> 19 CH3 2 LEU CD1 7 0 15.035 >> >>> DUM 0 15.035; qtot 1 >> >>> 20 CH3 2 LEU CD2 7 0 15.035 >> >>> DUM 0 15.035; qtot 1 >> >>> >> >>> >> >>> For A->L : >> >>> [ atoms ] >> >>> 17 CH3 2 ALA CB 6 0 15.035 >> >>> CH2 0 14.027; qtot 1 >> >>> 60 DUM 6 DUM DUM 24 0 13.019 >> >>> CH1 0 13.019 >> >>> 61 DUM 6 DUM DUM 24 0 15.035 >> >>> CH3 0 15.035 >> >>> 62 DUM 6 DUM DUM 24 0 15.035 >> >>> CH3 0 15.035 >> >>> >> >>> thanks for help >> >>> >> >>> LQ >> >>> -------------- next part -------------- >> >>> A non-text attachment was scrubbed... >> >>> Name: topol_A2L.top >> >>> Type: application/x-extension-top >> >>> Size: 15230 bytes >> >>> Desc: not available >> >>> Url : >> >>> http://www.gromacs.org/pipermail/gmx-users/attachments/20080616/562fa99f/topol_A2L.bin >> >>> -------------- next part -------------- >> >>> A non-text attachment was scrubbed... >> >>> Name: topol_L2A.top >> >>> Type: application/x-extension-top >> >>> Size: 15189 bytes >> >>> Desc: not available >> >>> Url : >> >>> http://www.gromacs.org/pipermail/gmx-users/attachments/20080616/562fa99f/topol_L2A.bin >> >>> >> >>> ------------------------------ >> >>> >> >>> _______________________________________________ >> >>> gmx-users mailing list >> >>> gmx-users@gromacs.org <mailto:gmx-users@gromacs.org> >> >>> http://www.gromacs.org/mailman/listinfo/gmx-users >> >>> Please search the archive at http://www.gromacs.org/search before >> >>> posting! >> >>> >> >>> End of gmx-users Digest, Vol 50, Issue 50 >> >>> ***************************************** >> >>> >> >> >> >> _______________________________________________ >> >> gmx-users mailing list gmx-users@gromacs.org >> >> <mailto:gmx-users@gromacs.org> >> >> http://www.gromacs.org/mailman/listinfo/gmx-users >> >> Please search the archive at http://www.gromacs.org/search before >> >> posting! >> >> Please don't post (un)subscribe requests to the list. Use the www >> >> interface or send it to [EMAIL PROTECTED] >> >> <mailto:[EMAIL PROTECTED]>. >> >> Can't post? Read http://www.gromacs.org/mailing_lists/users.php >> >> >> > >> > _______________________________________________ >> > gmx-users mailing list gmx-users@gromacs.org >> > <mailto:gmx-users@gromacs.org> >> > http://www.gromacs.org/mailman/listinfo/gmx-users >> > Please search the archive at http://www.gromacs.org/search before >> > posting! >> > Please don't post (un)subscribe requests to the list. Use the www >> > interface or send it to [EMAIL PROTECTED] >> > <mailto:[EMAIL PROTECTED]>. >> > Can't post? Read http://www.gromacs.org/mailing_lists/users.php >> > >> >> -- >> ======================================== >> >> Justin A. Lemkul >> Graduate Research Assistant >> Department of Biochemistry >> Virginia Tech >> Blacksburg, VA >> jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080 >> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin >> >> ======================================== >> >> _______________________________________________ >> gmx-users mailing list gmx-users@gromacs.org >> <mailto:gmx-users@gromacs.org> >> http://www.gromacs.org/mailman/listinfo/gmx-users >> Please search the archive at http://www.gromacs.org/search before posting! >> Please don't post (un)subscribe requests to the list. Use the www >> interface or send it to [EMAIL PROTECTED] >> <mailto:[EMAIL PROTECTED]>. >> Can't post? Read http://www.gromacs.org/mailing_lists/users.php >> >> >> >> >> ------------------------------------------------------------------------ >> >> _______________________________________________ >> gmx-users mailing list gmx-users@gromacs.org >> http://www.gromacs.org/mailman/listinfo/gmx-users >> Please search the archive at http://www.gromacs.org/search before posting! >> Please don't post (un)subscribe requests to the list. Use the www >> interface or send it to [EMAIL PROTECTED] >> Can't post? Read http://www.gromacs.org/mailing_lists/users.php > > -- > ======================================== > > Justin A. Lemkul > Graduate Research Assistant > Department of Biochemistry > Virginia Tech > Blacksburg, VA > jalemkul[at]vt.edu | (540) 231-9080 > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin > > ======================================== > > _______________________________________________ > gmx-users mailing list gmx-users@gromacs.org > http://www.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at http://www.gromacs.org/search before posting! > Please don't post (un)subscribe requests to the list. Use the www interface > or send it to [EMAIL PROTECTED] > Can't post? Read http://www.gromacs.org/mailing_lists/users.php > _______________________________________________ gmx-users mailing list gmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to [EMAIL PROTECTED] Can't post? 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