Re: [gmx-users] Fwd: Bad performance in free energy calulations
Hi, somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. One minor point is that your duplication of atomtypes (with i and m prefixes) seems pretty redundant to me. Cheers, Hannes. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
Hi, mdrun doesn't see any problems, but if something else is reporting 25% utilization then that probably means you have something else running on your machine, which is a terrible idea for running mdrun. You should expect some slowdown wrt to the non-free-energy version of the run - the implementation of the short-ranged loops for the perturbed atoms is not as great as the rest. Mark On Tue, May 19, 2015 at 3:13 PM Julian Zachmann frankjulian.zachm...@uab.cat wrote: Dear Gromacs users, I want to do free energy calculations following this http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/index.html tutorial. My system contains a GPCR, membrane, small ligand, solvate - in total 60.000 atoms. I want to perturb the ligand (31 atoms, 3 hydrogen atoms get converted to dummy atoms, one carbon atom get converted to a carbon atom, the other 27 ligand atoms just change slightly their charges). Apart from the perturbation and an extra simulated annealing step in the equilibration, I am following the tutorial as close as possible. My calculations work, but the computer performance is really bad. I am using only 8 processors for each Lambda, so domain decomposition is not really an issue (see below) but the CPUs run with only 25% load. Which could be the reason? Any ideas? I have made all files available under this link https://drive.google.com/folderview?id=0B2M9aqeJrxnYfjRLbzZ0VkFBTlFraEJaWWJ3MzVSaHlUN2cyVzV6X2ZibjRkek81UVM5S0kusp=sharing . Thank you very much for your help!! Julian D O M A I N D E C O M P O S I T I O N S T A T I S T I C S av. #atoms communicated per step for force: 2 x 74451.3 av. #atoms communicated per step for LINCS: 2 x 4495.3 Average load imbalance: 2.9 % Part of the total run time spent waiting due to load imbalance: 1.4 % Steps where the load balancing was limited by -rdd, -rcon and/or -dds: X 2 % R E A L C Y C L E A N D T I M E A C C O U N T I N G On 8 MPI ranks Computing: Num Num CallWall time Giga-Cycles Ranks Threads Count (s) total sum% - Domain decomp. 81150 3.136 65.226 0.3 DD comm. load 81150 0.208 4.335 0.0 DD comm. bounds81150 0.257 5.355 0.0 Neighbor search81151 11.329235.608 1.2 Comm. coord. 81 4850 11.368236.425 1.2 Force 81 5001 466.392 9699.934 50.6 Wait + Comm. F 81 5001 10.598220.418 1.2 PME mesh 81 5001 386.976 8048.244 42.0 NB X/F buffer ops. 81 14701 1.670 34.724 0.2 Write traj.81 3 0.133 2.768 0.0 Update 81 5001 1.474 30.664 0.2 Constraints81 10002 20.387423.998 2.2 Comm. energies 81501 2.255 46.891 0.2 Rest 4.983103.631 0.5 - Total921.165 19158.221 100.0 - Breakdown of PME mesh computation - PME redist. X/F81 15003 134.013 2787.183 14.5 PME spread/gather 81 20004 179.277 3728.576 19.5 PME 3D-FFT 81 20004 22.603470.092 2.5 PME 3D-FFT Comm. 81 20004 47.072979.004 5.1 PME solve Elec 81 10002 3.941 81.965 0.4 - Core t (s) Wall t (s)(%) Time: 3693.315 921.165 400.9 (ns/day)(hour/ns) Performance:0.938 25.583 Finished mdrun on rank 0 Tue May 19 14:01:45 2015 -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit
Re: [gmx-users] Fwd: Bad performance in free energy calulations
somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. Minor point - if you are taking the difference between two mutations (say, with and without a ligand), then it's better to leave the masses untouched -- any contribution will cancel. There are some weird issues with changing masses in the constraint terms and their contribution to the free energies that need to be accounted for post-hoc. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
On 5/19/15 12:12 PM, Hannes Loeffler wrote: On Tue, 19 May 2015 12:03:41 -0400 Michael Shirts mrshi...@gmail.com wrote: Yep, that's what I generally do. Almost all alchemical changes involve a difference in two calculations (since the alchemical change itself is unphysical). Even one-calculation solvation free energy calculations are actually calculating the difference in free energy from liquid to vapor state. This reminds me: there was recently a discussion around couple-moltype on this list. My understanding is that this can be used for absolute free energies. But what I really want to make sure is this: as far as I can see in the code and I think the manual says that too is that when couple-moltype is not set in the .mdp none of the other couple- parameters have any effect should I set any of the to something. Do I get this right? Right, they're ignored. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
On Tue, 19 May 2015 17:48:17 +0200 Julian Zachmann frankjulian.zachm...@uab.cat wrote: Concerning the changes of the atom types: the changes in the charges are really small and the results will probably be the same if I would not convert the whole ligand, just the 4 atoms which are changing. However, as i had both ligands parametrised, I thought it would be a good idea to really convert the whole ligand from one to the other, and change all charges on all atoms. That's not what I meant. I was wondering why you define a, say, ic3 type and an mc3 type. They are identical! The charges are explicitly listed for both states so I think the atom types only affect the vdW terms. Cheers, Hannes. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
On Tue, 19 May 2015 11:37:11 -0400 Michael Shirts mrshi...@gmail.com wrote: somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. Minor point - if you are taking the difference between two mutations (say, with and without a ligand), then it's better to leave the masses untouched -- any contribution will cancel. There are some weird issues with changing masses in the constraint terms and their contribution to the free energies that need to be accounted for post-hoc. So you suggest to leave the mass lambdas simply at their initial (or final) value to be safe in case constraints are involved (and I am too lazy to check)? -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
Hello Hannes, As Michael said it is better to leave most things untouched and just change VDW and LJ - at least this is what I have been reading so far. Concerning the changes of the atom types: the changes in the charges are really small and the results will probably be the same if I would not convert the whole ligand, just the 4 atoms which are changing. However, as i had both ligands parametrised, I thought it would be a good idea to really convert the whole ligand from one to the other, and change all charges on all atoms. Probably it won't really make any difference. All the best, Julian 2015-05-19 17:37 GMT+02:00 Michael Shirts mrshi...@gmail.com: somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. Minor point - if you are taking the difference between two mutations (say, with and without a ligand), then it's better to leave the masses untouched -- any contribution will cancel. There are some weird issues with changing masses in the constraint terms and their contribution to the free energies that need to be accounted for post-hoc. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Julian Zachmann Laboratori de Medicina Computacional Unitat de Bioestadistica. Facultat de Medicina Universitat Autonoma de Barcelona 08193 Bellaterra (Barcelona). Spain Phone: (3493) 581 2797 Fax: (3493) 581 2344 E-mail: frankjulian.zachm...@uab.cat http://lmc.uab.es -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
As Michael said it is better to leave most things untouched and just change VDW and LJ - at least this is what I have been reading so far. Well, I didn't quite say this. Changes in the bonded terms do not entirely cancel. Changes in masses do 100% cancel because of the seperability of momenta and position, and the masses only contributed to the total energy through the momenta. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
Yep, that's what I generally do. Almost all alchemical changes involve a difference in two calculations (since the alchemical change itself is unphysical). Even one-calculation solvation free energy calculations are actually calculating the difference in free energy from liquid to vapor state. On Tue, May 19, 2015 at 11:58 AM, Hannes Loeffler hannes.loeff...@stfc.ac.uk wrote: On Tue, 19 May 2015 11:37:11 -0400 Michael Shirts mrshi...@gmail.com wrote: somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. Minor point - if you are taking the difference between two mutations (say, with and without a ligand), then it's better to leave the masses untouched -- any contribution will cancel. There are some weird issues with changing masses in the constraint terms and their contribution to the free energies that need to be accounted for post-hoc. So you suggest to leave the mass lambdas simply at their initial (or final) value to be safe in case constraints are involved (and I am too lazy to check)? -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
Concerning the changes of the atom types: the changes in the charges are really small and the results will probably be the same if I would not convert the whole ligand, just the 4 atoms which are changing. However, as i had both ligands parametrised, I thought it would be a good idea to really convert the whole ligand from one to the other, and change all charges on all atoms. That's not what I meant. I was wondering why you define a, say, ic3 type and an mc3 type. They are identical! The charges are explicitly listed for both states so I think the atom types only affect the vdW terms. There is no specific reason for it. After the parametrisation of the ligands I just took for both of them all atom types and use them for the ligand conversion - whether they are identical, only slightly different, or not. 2015-05-19 18:00 GMT+02:00 Hannes Loeffler hannes.loeff...@stfc.ac.uk: On Tue, 19 May 2015 17:48:17 +0200 Julian Zachmann frankjulian.zachm...@uab.cat wrote: Concerning the changes of the atom types: the changes in the charges are really small and the results will probably be the same if I would not convert the whole ligand, just the 4 atoms which are changing. However, as i had both ligands parametrised, I thought it would be a good idea to really convert the whole ligand from one to the other, and change all charges on all atoms. That's not what I meant. I was wondering why you define a, say, ic3 type and an mc3 type. They are identical! The charges are explicitly listed for both states so I think the atom types only affect the vdW terms. Cheers, Hannes. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Julian Zachmann Laboratori de Medicina Computacional Unitat de Bioestadistica. Facultat de Medicina Universitat Autonoma de Barcelona 08193 Bellaterra (Barcelona). Spain Phone: (3493) 581 2797 Fax: (3493) 581 2344 E-mail: frankjulian.zachm...@uab.cat http://lmc.uab.es -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] Fwd: Bad performance in free energy calulations
On Tue, 19 May 2015 12:03:41 -0400 Michael Shirts mrshi...@gmail.com wrote: Yep, that's what I generally do. Almost all alchemical changes involve a difference in two calculations (since the alchemical change itself is unphysical). Even one-calculation solvation free energy calculations are actually calculating the difference in free energy from liquid to vapor state. This reminds me: there was recently a discussion around couple-moltype on this list. My understanding is that this can be used for absolute free energies. But what I really want to make sure is this: as far as I can see in the code and I think the manual says that too is that when couple-moltype is not set in the .mdp none of the other couple- parameters have any effect should I set any of the to something. Do I get this right? Many thanks for the answers, Hannes. On Tue, May 19, 2015 at 11:58 AM, Hannes Loeffler hannes.loeff...@stfc.ac.uk wrote: On Tue, 19 May 2015 11:37:11 -0400 Michael Shirts mrshi...@gmail.com wrote: somewhat off-topic but I wonder why in your free energy protocol you only vary the vdW and electrostatic lambdas. What about the others? Your mutation also transforms bonded terms and masses. Minor point - if you are taking the difference between two mutations (say, with and without a ligand), then it's better to leave the masses untouched -- any contribution will cancel. There are some weird issues with changing masses in the constraint terms and their contribution to the free energies that need to be accounted for post-hoc. So you suggest to leave the mass lambdas simply at their initial (or final) value to be safe in case constraints are involved (and I am too lazy to check)? -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
