Hello Sir Benson, We are using Supermicro SYS-1028R-WC1R Server with 2 x 2.2Ghz 12-Core Intel Processors (4 x 8GB DDR4) with a single node only. Ideally, to reach the microsecond simulation of GPCR-membrane simulation in all-atom, we will be needing a computer cluster with at least 200 parallel nodes system. But even with a 50-100 parallel nodes, we will reach the simulation time for a month, although we know that this is challenging for us here in the Philippines.
The specialized super-computer cluster Anton is an example of hardware that have reached more than 100 microseconds simulation of the all-atom GPCR-membrane simulation in a month of total CPU time. It has 512 processing nodes. Best regards, Mac Kevin E. Braza On Tue, Apr 2, 2019, 12:40 AM Benson Muite <benson_mu...@emailplus.org> wrote: > Hi Mac Kevin E. Braza, > > What hardware are you using? What kind of hardware would be needed to do > a full simulation instead of a coarse-grained one? > > Regards, > > Benson > > On 4/1/19 6:49 PM, João Henriques wrote: > > GPCR + membrane systems are notoriously big systems to work with for most > > research groups, regardless of your location on the map. Even in > > "privileged Europe" many research groups would struggle to produce > > microsecond long atomistic simulations of this system within a short > period > > of time. Moreover, "privileged Europe" is also home to significant > computer > > resource discrepancies among its member countries. This is actually one > of > > the main reasons why your group's CG model is so popular :) > > > > On Mon, Apr 1, 2019 at 5:09 PM P C Kroon <p.c.kr...@rug.nl> wrote: > > > >> Hi, > >> > >> I work in privileged Europe, so it’s good for me to get a reality check > >> once every while. Thanks. > >> > >> Coarse graining molecules for Martini is not too hard. There should be > >> some tutorials on cgmartini.nl that should help you get underway. You > >> will, however, run into the problems I mentioned, and you will need to > do > >> extensive validation on the topologies of your ligands. Again, it > depends > >> on your exact research question: if you’re doing high-throughput like > >> screening, qualitative models might be good enough. Also see T Bereau’s > >> automartini. > >> > >> Peter > >> > >> From: Mac Kevin Braza > >> Sent: 01 April 2019 16:06 > >> To: gmx-us...@gromacs.org > >> Cc: gromacs.org_gmx-users@maillist.sys.kth.se > >> Subject: Re: [gmx-users] Coarse-grained Protein-ligand simulations > >> > >> Dear Sir Peter Kroon, > >> > >> We are currently maximizing the computer capabilities to reach > microsecond, > >> but to reach 1 microsecond in our lab, it would take me at least 6 > months > >> to finish all one microsecond. > >> We do not have that high level capacities here in the Philippines to > reach > >> it. Membrane proteins are > >> typically longer, with all the lipid bilayers, solvent, and ions > present on > >> top of the protein. > >> We will need more powerful computers in this part. > >> > >> I found few works from literature on the protein-ligand representation > in > >> Coarse-grained. > >> We found several papers but they are either have vague methodology in > >> describing the ligand coarse-graining method and/or not necessarily have > >> the same research problem > >> as we want to explore. > >> > >> All in all, we will finish the simulation in all-atom as long as we can, > >> and still be hopeful with > >> the coarse-graining method. What we explored as in the present is the > >> CHARMM-GUI Martini Maker, > >> yet they do not include the drug ligands in representing them in > >> coarse-grained. I still have to search for other means > >> to do this. Thank you very much! > >> > >> Best regards, > >> Mac Kevin E. Braza > >> > >> On Mon, Apr 1, 2019 at 5:59 PM Peter Kroon <p.c.kr...@rug.nl> wrote: > >> > >>> Hi, > >>> > >>> that's probably a tough cookie. My first instinct would be to just > apply > >>> a more hardware, and do it all atomistically. A microsecond should be > >>> within reach. Whether it's enough is a separate matter. The problem is > >>> that most CG representations don't get the shape of both your pocket > and > >>> ligand exactly right, producing unreliable answers. In addition, in > most > >>> CG FFs hydrogen bonds are isotropic and not specific enough for this > >>> kind of problem. > >>> > >>> If "more hardware" is not an option you'll need to dive into literature > >>> to see if people did CG protein-ligand binding/docking/unbinding > >>> (depening on research question). I would also be very skeptical of any > >>> (absolute) kinetics produced by CG simulations. > >>> > >>> As a last ditch effort you could look into multiscaling, but that's a > >>> research topic in its own. > >>> > >>> > >>> Peter > >>> > >>> > >>> On 01-04-19 11:49, Mac Kevin Braza wrote: > >>>> Thank you Prof. Lemkul, > >>>> > >>>> I appreciate your comment on this part. > >>>> > >>>> Sir Peter Kroon, > >>>> > >>>> We want to do the coarse-grained MD simulation to access long > timescale > >>>> events of the > >>>> effect of the ligand binding to the GPCR, at least microsecond . For > >> now, > >>>> the most accessible means for us is to > >>>> do the CGMD. But we are currently being cornered in choosing which > >> set-up > >>>> will best suit, and > >>>> if it will allow us to see these events. We are looking also in the > >>>> possibility of coarse-graining > >>>> the ligand, and if you can share your expertise in coarse-graining > also > >>> the > >>>> ligand that would be great. > >>>> I appreciate this Sir Kroon, thank you very much! > >>>> > >>>> Best regards, > >>>> Mac Kevin E. Braza > >>>> > >>>> On Mon, Apr 1, 2019 at 5:07 PM Peter Kroon <p.c.kr...@rug.nl> wrote: > >>>> > >>>>> If I may chip in: It really depends on what you're studying, and what > >>>>> forcefield you're using to do it. Unfortunately there is no FF that > >>>>> reproduces all behaviour accurately. The art is in picking one that > >> (at > >>>>> least) reproduces what you're interested in. > >>>>> > >>>>> > >>>>> Peter > >>>>> > >>>>> On 29-03-19 17:26, Justin Lemkul wrote: > >>>>>> On 3/29/19 9:17 AM, Mac Kevin Braza wrote: > >>>>>>> Thank you Professor Lemkul, > >>>>>>> > >>>>>>> But would you suggest on how can I coarse-grained the ligand I am > >>>>>>> using? I > >>>>>>> have been searching resources online but they do not work in our > >> part. > >>>>>> I don't work with CG simulations, so I'm not much help. I would > think > >>>>>> that a CG parametrization of a ligand would remove all the detail > >>>>>> you'd normally want to see in terms of ligand-protein interactions. > >>>>>> > >>>>>> -Justin > >>>>>> > >>>>>>> I hope you can help us. Thank you Prof. Lemkul! > >>>>>>> > >>>>>>> Best regards, > >>>>>>> Mac Kevin E. Braza > >>>>>>> > >>>>>>> On Fri, Mar 29, 2019, 8:59 PM Justin Lemkul <jalem...@vt.edu> > >> wrote: > >>>>>>>> On 3/29/19 3:32 AM, Mac Kevin Braza wrote: > >>>>>>>>> Hello everyone, > >>>>>>>>> > >>>>>>>>> I am simulating a coarse-grained model of a membrane protein > >> (GPCR) > >>> in > >>>>>>>>> lipid bilayer and an all-atom ligand octopamine. I build the > >>> protein, > >>>>>>>>> solutes, and membrane in the web server CHARMM-GUI. While, I > added > >>> the > >>>>>>>>> ligand to the protein complex manually using the same coordinates > >>>>>>>>> of the > >>>>>>>>> coarse-grained protein model. > >>>>>>>>> > >>>>>>>>> I used the GROMACS input files from the output of CHARMM-GUI to > >>>>>>>>> simulate > >>>>>>>>> the system. I include the LIGAND.ITP (from the PRODRG Server) to > >> the > >>>>>>>>> system.top and added the atom indexes in the index.ndx file. > >>>>>>>> Don't do this. An atomistic representation of a ligand and a CG > >>>>>>>> representation of everything else is incompatible. Mixing and > >>> matching > >>>>>>>> force fields is never a good idea. Moreover, PRODRG produces > >>> topologies > >>>>>>>> that are known to be unsuitable for MD simulations. > >>>>>>>> > >>>>>>>>> However, when I proceed with the second part of equilibration, > the > >>>>>>>>> following errors occurred. > >>>>>>>>> > >>>>>>>>> *Command line*: > >>>>>>>>> gmx grompp -f step6.2_equilibration.mdp -o > >>>>>>>>> step6.2_equilibration.tpr > >>>>>>>> -c > >>>>>>>>> step6.1_equilibration.gro -p system.top -n index.ndx > >>>>>>>>> > >>>>>>>>> Setting the LD random seed to 1722366284 > >>>>>>>>> Generated 2391 of the 4656 non-bonded parameter combinations > >>>>>>>>> Excluding 1 bonded neighbours molecule type 'PROA_P' > >>>>>>>>> Excluding 1 bonded neighbours molecule type 'POPC' > >>>>>>>>> Excluding 1 bonded neighbours molecule type 'W' > >>>>>>>>> Excluding 1 bonded neighbours molecule type 'NA' > >>>>>>>>> Excluding 1 bonded neighbours molecule type 'CL' > >>>>>>>>> Excluding 3 bonded neighbours molecule type 'LIG' > >>>>>>>>> Velocities were taken from a Maxwell distribution at 303.15 K > >>>>>>>>> Removing all charge groups because cutoff-scheme=Verlet > >>>>>>>>> > >>>>>>>>> ------------------------------------------------------- > >>>>>>>>> Program gmx grompp, VERSION 5.1.4 > >>>>>>>>> Source code file: > >>>>>>>>> /home/gromacs-5.1.4/src/gromacs/gmxpreprocess/readir.c, > >>>>>>>>> line: 2690 > >>>>>>>>> > >>>>>>>>> Fatal error: > >>>>>>>>> 20 atoms are not part of any of the T-Coupling groups > >>>>>>>>> For more information and tips for troubleshooting, please check > >> the > >>>>>>>> GROMACS > >>>>>>>>> website at http://www.gromacs.org/Documentation/Errors > >>>>>>>>> ------------------------------------------------------- > >>>>>>>>> > >>>>>>>>> The 20 atoms described the ligand I placed inside the > >>> protein-membrane > >>>>>>>>> complex. I want to know if where can this error originate and how > >>>>>>>>> can we > >>>>>>>>> fix them? > >>>>>>>> This simply means you haven't specified the ligand anywhere in > >>> tc-grps. > >>>>>>>> But again, back up and reevaluate your approach, which is far more > >>>>>>>> problematic than this simple index group issue. > >>>>>>>> > >>>>>>>> -Justin > >>>>>>>> > >>>>>>>> -- > >>>>>>>> ================================================== > >>>>>>>> > >>>>>>>> Justin A. Lemkul, Ph.D. > >>>>>>>> Assistant Professor > >>>>>>>> Office: 301 Fralin Hall > >>>>>>>> Lab: 303 Engel Hall > >>>>>>>> > >>>>>>>> Virginia Tech Department of Biochemistry > >>>>>>>> 340 West Campus Dr. > >>>>>>>> Blacksburg, VA 24061 > >>>>>>>> > >>>>>>>> jalem...@vt.edu | (540) 231-3129 > >>>>>>>> http://www.thelemkullab.com > >>>>>>>> > >>>>>>>> ================================================== > >>>>>>>> > >>>>>>>> -- > >>>>>>>> Gromacs Users mailing list > >>>>>>>> > >>>>>>>> * Please search the archive at > >>>>>>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List > before > >>>>>>>> posting! > >>>>>>>> > >>>>>>>> * Can't post? 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