On Thu, May 18, 2017 at 6:48 PM, Justin Lemkul <jalem...@vt.edu> wrote:
> > > On 5/17/17 8:55 AM, abhisek Mondal wrote: > >> This time I think I got ligand restrained successfully during the umbrella >> sampling. I have removed the restrain from protein, as per your advice. >> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used >> pull_rate1=0.0. >> I have uploaded the trajectory movie (and other mdp files) in the >> following >> link: >> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0 >> >> However, I'm facing a problem. Due to the withdrawal of the position >> restrain of protein. The protein and ligand (together) is moving around >> the >> box and resulting in "Distance of pull group 1 (10.441990 nm) is larger >> than 0.49 times the box size (10.646989)" error. >> >> As per the video I have uploaded, if I assume this approach worked, then >> how can I avoid this error ? Is there any way to make sure the >> protein-ligand remains in the middle of the box (or nearby). I have taken >> pretty large box compared to the protein structure from the beginning. >> >> Please suggest me a way out. >> >> > Use a larger box or use direction-periodic geometry. For the sake of computational power I'm leaning towards direction-periodic geometry. However, from the mailing list entries I found out that pressure coupling should not be used for this kind of geometry setup. NVT coupling with no velocity generation is what I'm opting for. There are a lot of doubt regarding the md_umbrella.mdp setup using NVT protocol. Would you please suggest if the code ( https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0) looks sensible ? Eagerly waiting for your opinion. > > -Justin > > > On Mon, May 15, 2017 at 5:48 PM, Justin Lemkul <jalem...@vt.edu> wrote: >> >> >>> >>> On 5/15/17 2:45 AM, abhisek Mondal wrote: >>> >>> On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul <jalem...@vt.edu> wrote: >>>> >>>> >>>> >>>>> On 5/11/17 9:21 AM, abhisek Mondal wrote: >>>>> >>>>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal < >>>>> abhisek.m...@gmail.com >>>>> >>>>>> >>>>>>> wrote: >>>>>> >>>>>> Hi, >>>>>> >>>>>> >>>>>>> Thank you for the explanation. It really cleared some concepts. But >>>>>>> I'm >>>>>>> still having my ligand moving in this step. I have modified the code >>>>>>> as: >>>>>>> ; Pull code >>>>>>> pull = umbrella >>>>>>> pull_ngroups = 1 >>>>>>> pull_group0 = Protein_chain_A >>>>>>> pull_group1 = ACO >>>>>>> pull_geometry = direction ; simple distance increase >>>>>>> pull_dim = Y Y Y ; not to allow ligand move along >>>>>>> other >>>>>>> dir >>>>>>> pull_rate1 = 0.0 >>>>>>> pull_k1 = 1000 ; kJ mol^-1 nm^-2 >>>>>>> pull_start = yes ; define initial COM distance > 0 >>>>>>> pull_vec1 = 0 0 -1 >>>>>>> >>>>>>> >>>>>>> Note that with "direction" geometry, only pull_vec1 is acting. >>>>>>> >>>>>> pull_dim >>>>> is ignored. >>>>> >>>>> The ligand was previously moving along x,y direction when I was using >>>>> >>>>> pull_dim = N N Y. So I changed it to Y in all direction and provided 0 >>>>>> >>>>>>> as >>>>>>> vector and pull_rate1=0.0, so that it does not move much. But at the >>>>>>> end >>>>>>> of a 10ns run, I see that the ligand is still moving as it was >>>>>>> earlier. >>>>>>> >>>>>>> It shows me: >>>>>>> >>>>>>> Pull group natoms pbc atom distance at start reference at t=0 >>>>>> 0 1132 936665 >>>>>> 1 59 1618 -1.555 -1.555 >>>>>> Is it ok withe negative value ? Anyway this setup is not working. >>>>>> >>>>>> >>>>>> Again you're trying to just apply the restraint to one dimension and >>>>>> it >>>>>> >>>>> looks to be fairly arbitrary. I already suggested using the vector >>>>> connecting the ligand COM with the binding site residues' COM and using >>>>> that as pull_vec1. Draw it out. It makes a lot more sense than trying >>>>> to >>>>> restrain only along one axis, which as I have said before, makes no >>>>> sense >>>>> in this case. >>>>> >>>>> Thank you for such detailed suggestion. >>>>> >>>>> I followed on as per your suggestion. Calculated COM of protein and >>>> Ligand. >>>> Calculated protein-lig vector (using COM) to be used for pulling (as >>>> pull_vec1). >>>> Pulling also achieved successfully. >>>> But after pulling, when I performed the brief npt_umbrella run with >>>> pull_rate1=0, I found the ligand is moving little bit. Could not >>>> understand >>>> what I have mistaken this time. >>>> So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and >>>> pull_vec1=as determined from COM calculations. Despite I found that the >>>> ligand is moving vigorously and got pulled away probably. >>>> I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for >>>> npt_umbrella), npt140.gro,md_umbrella run video in the following link: >>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0 >>>> >>>> >>>> Am I still missing some drastic steps ? Please suggest me if I do. I'm >>>> totally lost here in this regard. >>>> >>>> >>>> Again, don't restrain the protein. I've said this multiple times. >>> >>> The pull setup looks reasonable. Maybe you just need a stronger force >>> constant, or you should not use the COM of the whole protein, instead the >>> COM of a few important residues (use an index group with gmx traj -ox >>> -com >>> to get its coordinates). If the specified vector is off, so too will be >>> the resulting biasing potential. >>> >>> -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. >>> >>> >> >> >> > -- > ================================================== > > 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. > -- Abhisek Mondal *Senior Research Fellow* *Structural Biology and Bioinformatics Division* *CSIR-Indian Institute of Chemical Biology* *Kolkata 700032* *INDIA* -- 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.