Alright. I'm trying as per your advice. Actually my system is pretty big and due to constraint of computation power it is taking me more time to test vector setup. I really appreciate your time. Thanks a lot for your suggestions.
One thing I'm worried about here. In previous mail, I mentioned the "distance at start" and "ref at t=0" is negative. What does the negative value signify, I mean how can distance be negative ? Is is due to my poorly given vector definition or something else ? 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. > > -Justin > > >>> I have choose my reaction coordinate to be along -Z axis and want to >>> apply >>> biasing potential accordingly with restraining the ligand movement. Can >>> you >>> please suggest where am I failing with this code ? >>> >>> Thank you. >>> >>> >>> >>> On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul <jalem...@vt.edu> wrote: >>> >>> >>>> >>>> On 5/8/17 10:00 AM, abhisek Mondal wrote: >>>> >>>> On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul <jalem...@vt.edu> wrote: >>>>> >>>>> >>>>> >>>>>> On 5/7/17 1:57 AM, abhisek Mondal wrote: >>>>>> >>>>>> Hi, >>>>>> >>>>>>> >>>>>>> For your ease of understanding regarding what is happening during >>>>>>> this >>>>>>> above said umbrella-mdrun, I have shared the trajectory video file >>>>>>> the >>>>>>> following link. >>>>>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0 >>>>>>> >>>>>>> Is this normal given that the mdp code being used ? I basically have >>>>>>> no >>>>>>> idea with this step, so please help me out. I'm using gromacs-4.6.2. >>>>>>> >>>>>>> >>>>>>> Your setup is incorrect. You're applying a biasing potential only >>>>>>> >>>>>> along >>>>>> z, so the ligand can move freely along x and y. A protein-ligand >>>>>> complex >>>>>> has spherical symmetry, so you should set the reaction coordinate to >>>>>> the >>>>>> vector connecting the ligand with some suitable subset of interacting >>>>>> protein residues. >>>>>> >>>>>> >>>>> >>>>> I don't get it. >>>>> We are trying not to move our configuration (generated after pulling >>>>> simulation) along the reaction coordinate, so for restraining we are >>>>> supposed to set pull_rate1=0.0. >>>>> >>>>> >>>> Of course. But you said set pull_k = 0 which does not make sense. The >>>> pulling rate *is* zero during umbrella sampling (no net displacement, >>>> restrain to the specified distance along the reaction coordinate) and >>>> pulling force constant should be non-zero. >>>> >>>> If applying biasing potential only along z is causing movement along x >>>> and >>>> >>>>> y then what if we apply the biasing potential along x,y,z ? Will it >>>>> cause >>>>> any good in restraining the ligand? >>>>> >>>>> >>>>> This is how it should be done. The reaction coordinate should be >>>> suitably defined based on the geometry of the system. As I suggested >>>> before, choose some representative residues in the active site as one >>>> group >>>> and the ligand as the other. Thus defines the reaction coordinate >>>> without >>>> any presupposition of anything being aligned with a Cartesian axis, >>>> which >>>> is rarely the case. >>>> >>>> Moreover, you said previously "A protein-ligand complex has spherical >>>> >>>>> symmetry, so you should set the reaction coordinate to the vector >>>>> connecting the ligand with some suitable subset of interacting protein >>>>> residues.". It is really unclear to me, could you please give me some >>>>> examples to understand it more simply? I had pulled the ligand along -z >>>>> axis, doesn't it mean that the reaction coordinate is to be that way ? >>>>> The >>>>> fact that I'm struggling with is to restrain the pull configurations >>>>> for >>>>> further sampling. >>>>> >>>>> >>>>> The reaction coordinate is whatever you define it to be. Whether or >>>> not >>>> pulling along the z-axis makes sense depends on the orientation of the >>>> system and the intrinsic geometry. In your case, it doesn't make sense. >>>> In my case (the tutorial, the unidirectional growth of an amyloid >>>> fibril) >>>> it does make sense to use a single Cartesian axis for the SMD portion >>>> and >>>> subsequent umbrella sampling. >>>> >>>> I'm really a beginner, so maybe I'm asking stupid questions. Please give >>>> >>>>> me >>>>> some advise. I'm really unable to decipher the scenario in comparison >>>>> to >>>>> your amyloid article in JPCB. >>>>> >>>>> >>>>> You should read the article to understand why I did what I did in the >>>> tutorial, and then move on to reading articles that are more similar to >>>> your case. These will be much more relevant to what you're doing. >>>> >>>> -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. >>>> >>>> >>> >>> >>> -- >>> Abhisek Mondal >>> >>> *Senior Research Fellow* >>> >>> *Structural Biology and Bioinformatics Division* >>> *CSIR-Indian Institute of Chemical Biology* >>> >>> *Kolkata 700032* >>> >>> *INDIA* >>> >>> >> >> >> > -- > ================================================== > > 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.