Re: [gmx-users] ligand falling out of active site during EM
Hi, Maybe as a note for any interested but unaware. In gromacs, the middle of the box is always the middle of the *rectangular* box defined by the first three numbers in the last line of the .gro file. Cheers, Tsjerk On 5/9/06, Anton Feenstra <[EMAIL PROTECTED]> wrote: Diane Fournier wrote:> Thank you !>> I think the problem was indeed with building the box, because I redid> the whole sequence on my drug-enzyme system (building the box with> editconf, putting the water with genbox, and then writing my .tpr > file with grompp) and ran the same (test) position restraint md run,> and this time, the ligand was inside. Will try minimisation again.For the record: you have almost certainly had problems with PBC. mdrun will always place molecules 'in the box' (see manual). If your complexhappens to be on the box edge, one molecule may end up at a differentside of the box.If, instead, your complex was in the middle of the box, as probably happend during your second setup sequence, pbc will not affect it, atleast not during EM when molecules tend not to move much.Note, that for different box shapes, the 'middle of the box' may not bewhat you expect. --Groetjes,Anton* NOTE: New Affiliation, Phone & Fax numbers (below) * _ ___| | || _ _ ___,| K. Anton Feenstra || / \ / \'| | | IBIVU/Bioinformatics - Vrije Universiteit Amsterdam ||( | )| | | De Boelelaan 1083 - 1081A HV Amsterdam - Netherlands || \_/ \_/ | | | Tel +31 20 59 87783 - Fax +31 20 59 87653 - Room P440 | | | [EMAIL PROTECTED] - www.few.vu.nl/~feenstra/ || | "If You See Me Getting High, Knock Me Down" (RHCP)||_|___|___gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-usersPlease don't post (un)subscribe requests to the list. Use thewww interface or send it to [EMAIL PROTECTED].Can't post? Read http://www.gromacs.org/mailing_lists/users.php-- Tsjerk A. Wassenaar, M.Sc.Groningen Biomolecular Sciences and Biotechnology Institute (GBB)Dept. of Biophysical ChemistryUniversity of GroningenNijenborgh 49747AG Groningen, The Netherlands+31 50 363 4336 ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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] ligand falling out of active site during EM
Diane Fournier wrote: Thank you ! I think the problem was indeed with building the box, because I redid the whole sequence on my drug-enzyme system (building the box with editconf, putting the water with genbox, and then writing my .tpr file with grompp) and ran the same (test) position restraint md run, and this time, the ligand was inside. Will try minimisation again. For the record: you have almost certainly had problems with PBC. mdrun will always place molecules 'in the box' (see manual). If your complex happens to be on the box edge, one molecule may end up at a different side of the box. If, instead, your complex was in the middle of the box, as probably happend during your second setup sequence, pbc will not affect it, at least not during EM when molecules tend not to move much. Note, that for different box shapes, the 'middle of the box' may not be what you expect. -- Groetjes, Anton * NOTE: New Affiliation, Phone & Fax numbers (below) * _ ___ | | | | _ _ ___,| K. Anton Feenstra | | / \ / \'| | | IBIVU/Bioinformatics - Vrije Universiteit Amsterdam | |( | )| | | De Boelelaan 1083 - 1081A HV Amsterdam - Netherlands | | \_/ \_/ | | | Tel +31 20 59 87783 - Fax +31 20 59 87653 - Room P440 | | | [EMAIL PROTECTED] - www.few.vu.nl/~feenstra/ | | | "If You See Me Getting High, Knock Me Down" (RHCP)| |_|___| ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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] ligand falling out of active site during EM
Thank you ! I think the problem was indeed with building the box, because I redid the whole sequence on my drug-enzyme system (building the box with editconf, putting the water with genbox, and then writing my .tpr file with grompp) and ran the same (test) position restraint md run, and this time, the ligand was inside. Will try minimisation again. Diane -Original Message- From: [EMAIL PROTECTED] on behalf of David Mobley Sent: Mon 5/8/2006 12:22 PM To: Discussion list for GROMACS users Subject: Re: [gmx-users] ligand falling out of active site during EM Diane, On 5/8/06, Diane Fournier <[EMAIL PROTECTED]> wrote: > Still on the same problem, I made a pr run on the complex, and had the same > result (ligand is out of the active site at time = 0.000 ps. Then I ran the > same pr run, but with dt = 0.001 ps with all coordinates output for my > trajectory. It turns out the ligand starts out of the active site, even if my > input coordinates have the ligand inside. What is happening ?? First, if you are doing energy minimization, dt does nothing... But second, double-check where it starts. For example, generate a tpr file and then use trjconv to convert your initial gro file to a pdb file and open it up with some viewer (i.e. pymol) (Or I guess use vmd to visualize your starting gro file). See if the ligand starts outside the binding site. If so, then it probably means you've done something in a funny order. For example, if you use editconf and genbox on just the protein before adding the ligand, well, those tools re-center teh protein in the box, so it will get shifted relative to the ligand (and hence the ligand will no longer be in the binding site). I think the solution to that is to use editconf or genbox on the system (protein+ligand), not just the protein. If that isn't the problem, it might be worth e-mailing the list exactly the steps you're following, and double-checking that the initial protein and ligand coordinates prior to setting up the system in GROMACS have the ligand in the binding site. David > > > -Original Message- > From: [EMAIL PROTECTED] on behalf of Diane Fournier > Sent: Fri 5/5/2006 3:05 PM > To: gmx-users@gromacs.org > Subject: [gmx-users] ligand falling out of active site during EM > > Hello ! > > I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John > Kerrigan's tutorial and everything worked fine. Now I'm trying with my system > but I get a problem : the ligand keeps falling out of the active site during > EM. I thought maybe it was a pbc problem and used comm-grps = protein in my > .mdp file, but I get the same result. I transformed the .gro input file to > .pdb to view it in pymol and the ligand is in the active site before > simulation. So it seems this happens during steepest descents EM. > > The ligand is a hybrid inhibitor containing a steroid moiety (estradiol) > linked to an adenosine-like moiety with a 13-methylene alkyl chain. > > Is there a way to keep/force the ligand in the active site during EM (maybe > using PR) ? > > Is this reflecting some physical phenomenon, ie the ligand has low affinity ? > > > > > ___ > gmx-users mailing listgmx-users@gromacs.org > http://www.gromacs.org/mailman/listinfo/gmx-users > 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 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 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] ligand falling out of active site during EM
Diane, On 5/8/06, Diane Fournier <[EMAIL PROTECTED]> wrote: Still on the same problem, I made a pr run on the complex, and had the same result (ligand is out of the active site at time = 0.000 ps. Then I ran the same pr run, but with dt = 0.001 ps with all coordinates output for my trajectory. It turns out the ligand starts out of the active site, even if my input coordinates have the ligand inside. What is happening ?? First, if you are doing energy minimization, dt does nothing... But second, double-check where it starts. For example, generate a tpr file and then use trjconv to convert your initial gro file to a pdb file and open it up with some viewer (i.e. pymol) (Or I guess use vmd to visualize your starting gro file). See if the ligand starts outside the binding site. If so, then it probably means you've done something in a funny order. For example, if you use editconf and genbox on just the protein before adding the ligand, well, those tools re-center teh protein in the box, so it will get shifted relative to the ligand (and hence the ligand will no longer be in the binding site). I think the solution to that is to use editconf or genbox on the system (protein+ligand), not just the protein. If that isn't the problem, it might be worth e-mailing the list exactly the steps you're following, and double-checking that the initial protein and ligand coordinates prior to setting up the system in GROMACS have the ligand in the binding site. David -Original Message- From: [EMAIL PROTECTED] on behalf of Diane Fournier Sent: Fri 5/5/2006 3:05 PM To: gmx-users@gromacs.org Subject: [gmx-users] ligand falling out of active site during EM Hello ! I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John Kerrigan's tutorial and everything worked fine. Now I'm trying with my system but I get a problem : the ligand keeps falling out of the active site during EM. I thought maybe it was a pbc problem and used comm-grps = protein in my .mdp file, but I get the same result. I transformed the .gro input file to .pdb to view it in pymol and the ligand is in the active site before simulation. So it seems this happens during steepest descents EM. The ligand is a hybrid inhibitor containing a steroid moiety (estradiol) linked to an adenosine-like moiety with a 13-methylene alkyl chain. Is there a way to keep/force the ligand in the active site during EM (maybe using PR) ? Is this reflecting some physical phenomenon, ie the ligand has low affinity ? ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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 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] ligand falling out of active site during EM
Still on the same problem, I made a pr run on the complex, and had the same result (ligand is out of the active site at time = 0.000 ps. Then I ran the same pr run, but with dt = 0.001 ps with all coordinates output for my trajectory. It turns out the ligand starts out of the active site, even if my input coordinates have the ligand inside. What is happening ?? -Original Message- From: [EMAIL PROTECTED] on behalf of Diane Fournier Sent: Fri 5/5/2006 3:05 PM To: gmx-users@gromacs.org Subject: [gmx-users] ligand falling out of active site during EM Hello ! I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John Kerrigan's tutorial and everything worked fine. Now I'm trying with my system but I get a problem : the ligand keeps falling out of the active site during EM. I thought maybe it was a pbc problem and used comm-grps = protein in my .mdp file, but I get the same result. I transformed the .gro input file to .pdb to view it in pymol and the ligand is in the active site before simulation. So it seems this happens during steepest descents EM. The ligand is a hybrid inhibitor containing a steroid moiety (estradiol) linked to an adenosine-like moiety with a 13-methylene alkyl chain. Is there a way to keep/force the ligand in the active site during EM (maybe using PR) ? Is this reflecting some physical phenomenon, ie the ligand has low affinity ? <>___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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] ligand falling out of active site during EM
Hi, I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John Kerrigan's tutorial and everything worked fine. Now I'm trying with my system but I get a problem : the ligand keeps falling out of the active site during EM. I thought maybe it was a pbc problem and used comm-grps = protein in my .mdp file, but I get the same result. I transformed the .gro input file to .pdb to view it in pymol and the ligand is in the active site before simulation. So it seems this happens during steepest descents EM. This means that it is lower energy for the ligand not to be in the binding site (at least, in its starting configuration) for some reason, assuming you have everything set up properly. Is there a way to keep/force the ligand in the active site during EM (maybe using PR) ? You could restrain it to stay in the binding site using distance restraints or position restraints or some such. But this may only mask some larger problem. Is this reflecting some physical phenomenon, ie the ligand has low affinity ? Hard to say. Where are you getting your starting coordinates? I doubt it is reflecting low affinity, as in my experience even low affinity ligands will stably stay in binding sites for relatively long times in MD, and definitely during energy minimization. It more likely means that your starting structure is not very good -- i.e. the ligand is sterically clashing with something in the binding site such that energy minimization moves the ligand to lower energy by removing the steric clashes and partly pushing the ligand out of the binding site. There are of course other possibilities... Your ligand parameters could be bad, etc. You could certainly solve the problem of it leaving during energy minimization by restraining it to stay in the binding site, but then it will probably just leave during MD, so I think you'd probably just be masking the problem. I would look carefully at your starting structure and doublecheck your parameters and so on. David ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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 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] ligand falling out of active site during EM
Title: ligand falling out of active site during EM Hello ! I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John Kerrigan's tutorial and everything worked fine. Now I'm trying with my system but I get a problem : the ligand keeps falling out of the active site during EM. I thought maybe it was a pbc problem and used comm-grps = protein in my .mdp file, but I get the same result. I transformed the .gro input file to .pdb to view it in pymol and the ligand is in the active site before simulation. So it seems this happens during steepest descents EM. The ligand is a hybrid inhibitor containing a steroid moiety (estradiol) linked to an adenosine-like moiety with a 13-methylene alkyl chain. Is there a way to keep/force the ligand in the active site during EM (maybe using PR) ? Is this reflecting some physical phenomenon, ie the ligand has low affinity ? ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users 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
