Re: [gmx-users] Deviations in free energies with slow growth (single and 3-step process)
David Thanks for your answer. I'm aware of that problem, but the idea was, that such a small system is very close to equilibrium on a 10ns timescale (maybe to optimistic). Actually, the thought behind it was to compare the results of the different free energy calculation methods. Now, if I assume slow growth has a systematic error of X because of non-equilibrium, I expect this error to occur more or less in the 1_step and in the 3_step calculation. However, I didn't mention, but I also did non-equilibrium tests (e.g. BAR) with this system and the deviation is exactly the same; means: BAR gives a difference of 7 kJ/mol for the ethane to methanol in 1_step hardcore and 3_step hc/sc/hc for the first and third being coulomb and the second being Lennard Jones. This actually puzzles me a bit, cause in the case of some tripeptide sidechain morphing (SER to ALA), the results of 1_step and 3_step perfectly match. I don't have to tell you, that the cycle together with the sim in gas phase gives a difference in free energy of solvation which is somewhat 15 kJ/mol away from the experiment, though. ;) For me the question arises, how to publish such shitty results. Do you think, 7 kJ/mol lies within the usual error of free energy calculations? If, one could never resolve reliably smaller free energy differences and the whole method won't be applicable for say drug screening or so. Regards Maik Goette, Dipl. Biol. Max Planck Institute for Biophysical Chemistry Theoretical computational biophysics department Am Fassberg 11 37077 Goettingen Germany Tel. : ++49 551 201 2310 Fax : ++49 551 201 2302 Email : mgoette[at]mpi-bpc.mpg.de mgoette2[at]gwdg.de WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/ David Mobley wrote: Maik, I simulated a switching process (slow growth TI) over 10ns of ethane to methanol with hardcore slow-growth in water (365 TIP4P waters,PME) and in vacuum. The thermodynamic cycle of this calculation yields a DeltaG, which is in perfect agreement with the experiment and other calculations. Slow growth is notoriously problematic, because it only gives the true free energy in the limit that you do it infinitely slowly. Otherwise you're really measuring nonequilibrium work values, which are connected to free energies but only in an average way (see the Jarzynski relationship for a more recent discussion of this). This could be a classic example of just because a method gives perfect agreement with experiment, you can't be sure it's giving the correct value for the force field. In other words, since force fields have their own limitations, we can't necessarily expect that when we do things right, we'll get optimal agreement with experiment. In some cases one may get better agreement with experiment by doing things *wrong* than by doing them right. i.e., suppose the correct value for the force field is actually off by 2 kJ/mol from the experimental value. If you make a protocol mistake, there's roughly a 50% chance (assuming the errors are randomly distributed!) that it will give you a value that's closer to the experimental value than your original value was. Now, when splitting this simulation into 3 steps (3x 3.2ns), where I switch the charges to zero in the first step (hardcore), morph the LJ and bonded in the second (softcore or hardcore) and switch the charges back on from zero in the third step (hardcore), all in solvent, the sum of the single contributions does NOT yield the same number as the single-step switching. In vacuum, the work values I get from the single step process and from adding up the values from the 3-step process perfectly match. The topologies for all systems are the same (except +/- water) for the 1-step and the 3-step simulations. Now I'm a bit puzzled and can't get an idea, where this difference in the solvated system may come from. I exclude a problem due to softcore, cause I also simulated the 3-step process all hardcore... Any ideas? I'm betting your problems are largely due to the fact you're doing slow growth. Again, see the Jarzynski relationship; I especially recommend his Phys. Rev. E. paper on convergence (2001?). It's also worth noting that slow growth transformations in different directions have different convergence properties, and with slow growth (interestingly enough) particle insertion actually converges more quickly than particle deletion. So you could try reversing the direction of the transformations and see what happens. But again, slow growth isn't recommended these days -- you should probably make sure you have a very good reason for doing it and are aware of the limitations. Best, David Regards -- Maik Goette, Dipl. Biol. Max Planck Institute for Biophysical Chemistry Theoretical computational biophysics department Am Fassberg 11 37077 Goettingen Germany Tel. : ++49 551 201 2310 Fax : ++49 551 201 2302 Email : mgoette[at]mpi-bpc.mpg.de mgoette2[at]gwdg.de WWW :
Re: [gmx-users] Re: installation problem for MAC OS
Hi Warner, I think this is a bug in the assembler/linker shipped with Leopard since the instructions are perfectly valid. In any case, I've worked around it in the release branch of CVS. Cheers, Erik On Feb 7, 2008, at 8:52 PM, Warner Yuen wrote: My apologies. I should have known better, but was too lazy to type all the configurations I tried. Its kind of like hitting the I'm feeling lucky button on Google. Anyway here's what I tried and always getting the following error: ld: in ../gmxlib/.libs/libgmx.a(nb_kernel204_ia32_sse.o), in section __TEXT,__text reloc 1: bad pc-rel vanilla relocation length collect2: ld returned 1 exit status make[3]: *** [grompp] Error 1 make[2]: *** [all-recursive] Error 1 make[1]: *** [all] Error 2 make: *** [all-recursive] Error 1 Compilers used: gcc version 4.0.1 (Apple Inc. build 5465) icc version 10.1.007 icc version 10.1.009 Gromacs: version 3.3.1 version 3.3.2 ./configure --prefix=/gromacs/gromacs_test ./configure --prefix=/gromacs/gromacs_test --disable-ia32-sse ./configure --prefix=/gromacs/gromacs_test --with-qmmm-cpmd -- disable-ia32-sse FFTW-3.1.1 using gcc ./configure --enable-float Warner Yuen Scientific Computing Consulting Engineer Apple Computer email: [EMAIL PROTECTED] Tel: 408.718.2859 Fax: 408.715.0133 On Feb 7, 2008, at 1:21 AM, [EMAIL PROTECTED] wrote: Message: 1 Date: Thu, 07 Feb 2008 08:20:44 +1100 From: Mark Abraham [EMAIL PROTECTED] Subject: Re: [gmx-users] Re: installation problem for MAC OS To: Discussion list for GROMACS users gmx-users@gromacs.org Message-ID: [EMAIL PROTECTED] Content-Type: text/plain; charset=ISO-8859-1; format=flowed Warner Yuen wrote: Hi Gromacs Users I've looked at trying to build Gromacs 3.3.2 with the pretty much the same configuration and suggestions as below, but I am still running into the ld error: ld: in ../gmxlib/.libs/libgmx.a(nb_kernel300_ia32_3dnow.o), in section __TEXT,__text reloc 1: bad pc-rel vanilla relocation length Any other suggestions? Computers are exacting, and so do you need to be when using them, and reporting problems. pretty much the same as another user configuring a 3rd-party modification of GROMACS could mean anything, even if the people you're trying to get free help from can be bothered making sense of that thread you quoted. They'll be much more interested in what configure command(s) you are actually using, on what hardware and on what OS with what results. :-) Mark ___ gmx-users mailing listgmx-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 listgmx-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] Pre-announcement: advanced Gromacs workshop at Stanford April 7-8
Hi, We've thought of doing an advanced simulation/modeling workshop at Stanford for a while, and finally settled on a date, although with a bit short notice :-) In any case, we will do a semi-advanced workshop at Stanford University in the US on April 7 8 with room for 30-35 people. The idea is that it's supposed to be a two-way communication event for people experienced with MD, and mixed talks on different free energy methods, parallelization, QM/MM, non-equilibrium simulations, and interesting new algorithms we might want to implement in the future. Consider this a pre-announcement that there will be a registration website available next week! There is no cost for workshop participation, but you will have to cover your own travel, accommodation (I will try to make a block reservation at the Stanford guest house which has very reasonable rates), and meals. Due to the limited size of the event we might have to give priority to people in the US and/or research themes that relates best to the workshop, but we are already discussing another workshop i Göttingen, Germany... Cheers, Erik ___ gmx-users mailing listgmx-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
Re: [gmx-users] g_dist producing inconsistent values
Hi, another quick and dirty tip (but at least it works !) is to generate a new trajectory using trjconv with a huge layer of vacuum on the Z direction (assuming your membrane normal is oriented along Z): you can do that with the -box option with a large value for Z. If you just put only the phosphorous atoms in there this won't generate a large file. Cheers, Patrick Alan Dodd a écrit : - Original Message From: David van der Spoel [EMAIL PROTECTED] To: Discussion list for GROMACS users gmx-users@gromacs.org Sent: Thursday, February 7, 2008 6:35:55 PM Subject: Re: [gmx-users] g_dist producing inconsistent values [EMAIL PROTECTED] wrote: I've since found the source of my problem - the program was measuring the (marginally shorter) distance across the PBC boundary, rather than the distance within the box. Unfortunately there doesn't seem to be a way to turn PBC images off (correct me if I'm wrong?), so I guess I'm going to do some jiggerypokery with the data and some math. Distance larger than half a box size are ill-defined anyway in a PBC simulation. -What do you mean? I'd assumed that simply having enough water separating a bilayer from its periodic image that no water 'saw' both bilayers would be sufficient; is this not the case? In some special cases you can do this, for instance within a protein it would work. I've implemented -nopbc options in some programs but not in g_dist yet. Please put it on the developer wishlist. on the wiki. -Done. Until then, I'm using g_traj -ox -com and doing the math with my own script. Many thanks for the various alternative techniques suggested. Never miss a thing. Make Yahoo your home page. http://www.yahoo.com/r/hs ___ gmx-users mailing listgmx-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 -- ___ Patrick FUCHS Equipe de Bioinformatique Genomique et Moleculaire INSERM U726, Universite Paris 7 Case Courrier 7113 2, place Jussieu, 75251 Paris Cedex 05, FRANCE Tel : +33 (0)1-44-27-77-16 - Fax : +33 (0)1-43-26-38-30 E-mail : [EMAIL PROTECTED] Web Site: http://www.ebgm.jussieu.fr/~fuchs ___ gmx-users mailing listgmx-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] Proline on OPLSSaa
Hi all, I'm trying to run a simulation of a proline in water tip5p with OPLSaa ff. The problem is that it has to be an N-acetyl-methoxyproline and i don't know how to add the methoxy. I've already tryed adding a new molecule to the .rtp file: [ APR ] [ atoms ] N opls_239 -0.776797 1 CA opls_246 -0.158578 2 C1 opls_058 0.954250 3 OS1 opls_062 -0.719990 4 C2 opls_235 0.808979 5 OS opls_059 -0.616492 6 CD opls_245 -0.150278 7 CB opls_136 -0.404838 8 HB1 opls_140 0.243450 9 CG opls_136 -0.450709 10 HB2 opls_140 0.226125 11 HG1 opls_140 0.223126 12 HG2 opls_140 0.242534 13 HD1 opls_140 0.239430 14 HD2 opls_140 0.239331 15 HA opls_140 0.262623 16 CE opls_468 -0.252649 17 HE1 opls_469 0.216104 18 HE2 opls_469 0.214466 19 HE3 opls_469 0.212312 20 OB opls_236 -0.606932 21 CF opls_135 -0.687405 22 HF1 opls_140 0.262125 23 HF2 opls_140 0.224449 24 HF3 opls_140 0.255303 25 [ bonds ] NCD NC2 C2 OB C2 CF CF HF1 CF HF2 CF HF3 CD HD1 CD HD2 CD CG CG HG1 CG HG2 CG CB CB HB1 CB HB2 CB CA CA N CA HA1 CA C1 C1 OS C1 OS1 OS1 CE CE HE1 CE HE1 CE HE3 and it works fine till i run grompp which says: ERROR 0 [file proline.top, line 182]: No default Ryckaert-Bell. types ERROR 0 [file proline.top, line 191]: No default Ryckaert-Bell. types ERROR 0 [file proline.top, line 193]: No default Ryckaert-Bell. types ERROR 0 [file proline.top, line 201]: No default Ryckaert-Bell. types This is my .top file: ; This is your topology file ; %E ; ; Include forcefield parameters #include ffoplsaa.itp ; Include water topology #include tip5p.itp #ifdef POSRES_WATER ; Position restraint for each water oxygen [ position_restraints ] ; i funct fcxfcyfcz 11 1000 1000 1000 #endif [ moleculetype ] ; Namenrexcl Protein 3 [ atoms ] ; nr type resnr residue atom cgnr charge mass typeB chargeB massB 1 opls_239 1APR N 1 -0.77679714.0067 ; qtot -0.7768 2 opls_246 1APR CA 2 -0.158578 12.011 ; qtot -0.9354 3 opls_058 1APR C1 30.95425 12.011 ; qtot 0.01887 4 opls_062 1APROS1 4 -0.7199915.9994 ; qtot -0.7011 5 opls_235 1APR C2 5 0.808979 12.011 ; qtot 0.1079 6 opls_059 1APR OS 6 -0.61649215.9994 ; qtot -0.5086 7 opls_245 1APR CD 7 -0.150278 12.011 ; qtot -0.6589 8 opls_136 1APR CB 8 -0.404838 12.011 ; qtot -1.064 9 opls_140 1APRHB1 90.24345 1.008 ; qtot -0.8203 10 opls_136 1APR CG 10 -0.450709 12.011 ; qtot -1.271 11 opls_140 1APRHB2 11 0.226125 1.008 ; qtot -1.045 12 opls_140 1APRHG1 12 0.223126 1.008 ; qtot -0.8218 13 opls_140 1APRHG2 13 0.242534 1.008 ; qtot -0.5792 14 opls_140 1APRHD1 140.23943 1.008 ; qtot -0.3398 15 opls_140 1APRHD2 15 0.239331 1.008 ; qtot -0.1005 16 opls_140 1APR HA 16 0.262623 1.008 ; qtot 0.1622 17 opls_468 1APR CE 17 -0.252649 12.011 ; qtot -0.09048 18 opls_469 1APRHE1 18 0.216104 1.008 ; qtot 0.1256 19 opls_469 1APRHE2 19 0.214466 1.008 ; qtot 0.3401 20 opls_469 1APRHE3 20 0.212312 1.008 ; qtot 0.5524 21 opls_236 1APR OB 21 -0.60693215.9994 ; qtot -0.05453 22 opls_135 1APR CF 22 -0.687405 12.011 ; qtot -0.7419 23 opls_140 1APRHF1 23 0.262125 1.008 ; qtot -0.4798 24 opls_140 1APRHF2 24 0.224449 1.008 ; qtot -0.2554 25 opls_140 1APRHF3 25 0.255303 1.008 ; qtot -6.101e-05 [ bonds ] ; aiaj functc0c1c2c3 1 2 1 1 5 1 1 7 1 2 3 1 2 8 1 3 4 1 3 6 1 417 1 521 1 522 1 710 1 714 1 715 1 8 9 1 810 1 811 1 1012 1 1013 1 1718 1 1720
[gmx-users] Re: Total Energy protein only
Quoting Yoshiko Santoso [EMAIL PROTECTED]: Dear Chris Neale, Thank you very much for answering my questions in gmx-users mailing list. (See Below) Hi gmx-users, Can anyone tell me how to find the total energy of the protein only (not the system)? You might try energygrp_excl SOL SOL or energygrp_excl SOL SOL SOL PROTEIN depending on what you want to acheive. THis will take care of all of the nonbonded interactions. Without knowing what you want this value for, I can only warn you against trying to use this value as a measure of how good the structure is. __ I have another question, I hope you can help me. I did the MD run with energy_excl, once the simulation is finished, where can I obtain the total energy of the protein only? What I put on mdp file is energy_excl = sol sol sol protein Is it by looking at the md.log? but where is it exactly to look? It is by g_energy (read the manual), but the value that is available is not what I believe that you expect it to be and I think that you may have missed the point of my suggestion. I think that you should back up and tell us what you want to do and why and then we can offer some better suggestions. You will have better chance to get a reply by posting to the list. Please post your reply under the same title as this email to the mailing list. Chris. I'm fairly new with GROMACS, so I hope you can help me. Thank you very much, -Yoshiko- Graduate Student ___ gmx-users mailing listgmx-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
Re: [gmx-users] Deviations in free energies with slow growth (single and 3-step process)
Maik, Thanks for your answer. I'm aware of that problem, but the idea was, that such a small system is very close to equilibrium on a 10ns timescale (maybe to optimistic). I am not sure the issue with slow growth is as simple as what timescale does it take for the system to equilibrate?. In particular, with repeated realizations of the same slow growth simulation (i.e. from different starting configurations) you should get a distribution of work values; the width of the distribution will be determined by how slowly you do the calculations. But I don't see any reason why this distribution should be that narrow even on 10 ns timescales. Actually, the thought behind it was to compare the results of the different free energy calculation methods. If you want to do that, instead of doing slow growth you may want to use the Jarzynski method to analyze output of slow growth simulations. Now, if I assume slow growth has a systematic error of X because of non-equilibrium, That's just the thing -- it won't have a systematic error. It will give you a distribution of different answers if you do it again and again, since it's nonequilibrium. For any particular simulation, you have no idea how the computed free energy will relate to the true free energy you would get if you were able to evaluate the free energy using i.e. the Jarzynski relation. Hence, it's not a systematic error, but rather a random error (from a particular distribution). I expect this error to occur more or less in the 1_step and in the 3_step calculation. However, I didn't mention, but I also did non-equilibrium tests (e.g. BAR) with this system and the deviation is exactly the same; Sorry, I'm unclear what you mean here. BAR is usually used to analyze results of equilibrium simulations (i.e., simulations run in equilibrium at distinct lambda values). There is of course the Crooks equation (generalization of Jarzynski) that looks like the BAR equation but is for nonequilibrium switching; is that what you're talking about? And I'm not clear what you mean when you say, I expect this error to occur more or less in the 1_step and in the 3_step calculation. means: BAR gives a difference of 7 kJ/mol for the ethane to methanol in 1_step hardcore and 3_step hc/sc/hc for the first and third being coulomb and the second being Lennard Jones. Oh, you mean using the Crooks relationship for computing free energies using nonequilibrium switching from ethane- methanol and methanol- ethane? Of the nonequilibrium approaches you've described that seems most reasonable. I think if you want me to comment further I'll probably need a table showing what exact calculations you've done, with a brief description of the protocols, and the results -- I'm getting a bit jumbled up about all of the different things you've tried. Is this supposed to be a methods comparison paper or something? This actually puzzles me a bit, cause in the case of some tripeptide sidechain morphing (SER to ALA), the results of 1_step and 3_step perfectly match. I don't have to tell you, that the cycle together with the sim in gas phase gives a difference in free energy of solvation which is somewhat 15 kJ/mol away from the experiment, though. ;) Again, if you do a particular slow growth simulation (what you're calling 1_step, I think?) and compare results with equilibrium simulations, or slow-growth broken into components, and manage to get perfect agreement, you're probably just lucky (or unlucky, depending on how you look at it). You could even try repeating the slow growth simulations from a different starting config -- I bet you'd get a different result, indicating agreement is coincidental. For me the question arises, how to publish such shitty results. Do you think, 7 kJ/mol lies within the usual error of free energy calculations? If, one could never resolve reliably smaller free energy differences and the whole method won't be applicable for say drug screening or so. This is of course why error analysis is essential. When I do these sorts of calculations I make sure the statistical uncertainty is much lower than 7 kJ/mol. As far as your results go, since I don't have enough detail on your protocol I just don't know. David Regards Maik Goette, Dipl. Biol. Max Planck Institute for Biophysical Chemistry Theoretical computational biophysics department Am Fassberg 11 37077 Goettingen Germany Tel. : ++49 551 201 2310 Fax : ++49 551 201 2302 Email : mgoette[at]mpi-bpc.mpg.de mgoette2[at]gwdg.de WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/ David Mobley wrote: Maik, I simulated a switching process (slow growth TI) over 10ns of ethane to methanol with hardcore slow-growth in water (365 TIP4P waters,PME) and in vacuum. The thermodynamic cycle of this calculation yields a DeltaG, which is in perfect agreement with the experiment and other calculations. Slow growth is notoriously problematic, because it only
[gmx-users] non bonded interactions
I turned off all non bonded interaction using the following: energygrp_excl = SOL SOL SOL Protein_A SOL Protein_B Protein_A Protein_B (where Protein_A and Protein_B, are the 2 molecules (peptides) in the box) I assume this will not affect excluded volume i.e I do not expect to see distances less that twice the radius of an atom. However, after my simulation I get the ff result for the distance between 2 alpha C atoms in Protein_A and Protein_B (using g_dist): 0.182811 0.221014 0.240868 0.279282 0.322291 0.334325 0.356991 0.357273 0.401965 The diameter of a C atom is about .3nm so I was surprised to see distances less than that. I'll appreciate any help. Regards John _ Need to know the score, the latest news, or you need your Hotmail®-get your fix. http://www.msnmobilefix.com/Default.aspx___ gmx-users mailing listgmx-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
