Re: [gmx-users] simulation with ligand at the active site
Previously, something like happened to me, the solution that worked for me was to use acpype (code.google.com/p/acpype) and Amber FF. In this way, you could rule out problems related to the prodrg parameters. Best regards, Aldo === Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com = --- El jue 28-abr-11, Justin A. Lemkul escribió: De: Justin A. Lemkul Asunto: Re: [gmx-users] simulation with ligand at the active site A: "Discussion list for GROMACS users" Fecha: jueves, 28 de abril de 2011, 1:02 onetwo wrote: > Hello Users, > > I have a query regarding simulation with the ligand. > > In my protein there are two ligands, one of them (coenzyme) is from the > crystal data, and other I have docked at the active site, while docking > it is showing good interaction with all the active site residues very > well. > I used GROMOS96 43a1 force field, and got the topology file made from > prodrg beta, using GROMOS 96.1 for both the ligands. PRODRG produces notoriously bad topologies. See, for instance: http://www.gromacs.org/Downloads/Related_Software/PRODRG#Tips > while doing equilibration I did, brendenson coupling on like > ; Berendsen temperature coupling is on in two groups > Tcoupl = V-rescale > tc-grps = Protein Non-Protein > tau_t = 0.1 0.1 > ref_t = 300 300 > > and in MD simulation also > ; Berendsen temperature coupling is on in two groups > Tcoupl = V-rescale > tc-grps = Protein Non-Protein > tau_t = 0.1 0.1 > ref_t = 300 300 > There could be some debate about these settings, and I do not know the best way to handle temperature coupling. It seems to me that if you have a ligand (or multiple) bound to a protein, the interactions between the protein and ligand(s) will be tightly coupled, such that you shouldn't lump the ligands into the "Non-Protein" group, which in this case likely comprises solvent. Maybe someone with more experience in these types of simulations can share some insight. > But after 1ns equibiration, one of the ligand (the one which I docked) > is going away from the active site and then I ran it for 4 ns further, > it has gone more far from the cavity. Following is the link to the snapshot > of the ligand at different time. > > https://picasaweb.google.com/118389174994698260649/Md_complex?authkey=Gv1sRgCMis2qry3cGj7AE#5600499037480314402 > > I want to ask if the change in the > position of ligand is justified with the parameters i have taken or it > if i have done something wrong? > Without providing the actual topology(ies) of the ligand(s) and a complete .mdp file, it is hard to say. But if you're using PRODRG output, I would suspect that it would be the culprit. -Justin > Thanks and Regards > > <http://sigads.rediff.com/RealMedia/ads/click_nx.ads/www.rediffmail.com/signatureline.htm@Middle?> > -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Docking
Before making a MD simulation you should try to explore different ways to analyze your docking results. For example, performing the same experiment with different docking programs and scoring functions (“consensus scoring”) and compare the results, is there consistency between them?. Now, if docking results are not successful in terms of prior knowledge of your system (is there structural information of your system? articles?), you could select several of the complex predicted by the docking program and make a MD simulation and free energy calculation, compare the results for each complex and verify if the results improve according to what you expected. However, as mentioned by Mark, simulations and calculations like these involve much computational resources and time. Best regards, Aldo === Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com = --- El mié 27-abr-11, Mark Abraham escribió: De: Mark Abraham Asunto: Re: [gmx-users] Docking A: "Discussion list for GROMACS users" Fecha: miércoles, 27 de abril de 2011, 5:27 On 4/27/2011 7:52 PM, mohsen ramezanpour wrote: Dear Mark Thank you for your reply.yes,you are right. Regarding question 2: I have a pdf file from "Docking Server" for sertraline-SERT example.Suppose this is a good docked state. In the other hand,I did what I explained in section 1 for sertraline and SERT.(by pymol and ...) Now, I want to check if I have docked sertraline to SERT correctly or not( by comparing with Docking server's one) How can I do that? Comparing MD-docked structures and otherwise-docked structures is easy - look at the RMS deviation of atom positions, to start with. However, a small or large deviation is not evidence that either docked structure bears any relationship to what happens in vivo. Do you have any suggestion for doing docking by gromacs? for example pulling code, MD , or SMD? People use these kinds of methods for good reasons. Time spent reading up on how and why is time well spent. Mark Thanks in advance On Wed, Apr 27, 2011 at 1:48 PM, Mark Abraham wrote: On 4/27/2011 7:05 PM, mohsen ramezanpour wrote: Dear Users I read so many emails to mailing list, there were important notes about docking but I couldn't extract a general result. Please let me know: 1-Can we dock a ligand to it's protein's binding pocket with Pymol and Gromacs as following? first:locating ligand outside and close to binding site manually in pymol and saving complex.pdb second:doing all steps for generating complex.top and complex.gro as Enzyme-Drug tutorial third:running md (with out any pull code and constraint),in the other words,full flexible system. I think drug can move freely and according to it's interaction with binding site can be attracted by binding site. reside for a distance time and then will come out of pocket. Am I right? In principle, yes, but it is wildly unlikely that you have a system that can bind and unbind reliably in the 100ns simulation range that you might be able to afford to run, and if you did happen to have one, what would you have learned? I know what discussed in mainling list about deffinition of "Docking". 2-I have some docked files by "Docking Server " for some of my drug-protein's complexes. now,I want to obtain them by doing MD in the above proccess.if I was successful then try to do that for other drugs which I don't have any docked pdb for them. How can I fit a trajectory with a typical pdb file? I don't understand what you are asking. Mark -- gmx-users mailing list gmx-users@gromacs.org http://lis
Re: [gmx-users] re: Acpype error
First of all, I don't know if this is the right forum to discuss issues related to acpype. You should try to contact the acpype team. I'm not an acpype expert but if I can help you, do not hesitate to contact me through my email. Some tips: Considering that python, openbabel and Ambertools are properly installed and if the test shows an error, then something is wrong with the installation. How do you download the program? By: "svn" or "wget " if you want I can send you a copy that I use and works well, so you can try to install it. Regards, Aldo======= Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com = --- El mar 12-abr-11, fancy2012 escribió: De: fancy2012 Asunto: [gmx-users] re: Acpype error A: gmx-users@gromacs.org Fecha: martes, 12 de abril de 2011, 0:57 Dear Prof. Aldo Segura-Cabrera, Thanks very much for your reply. I just download the package of Acpype, and I ran ../acpype.py -i FFF.pdb to test acpype.py, but then I got the error. Amber11 and AmberTools 1.4 have been successfully installed on the computer. I have read the installation instruction, I find it is only creating a linker of acpype.py, I do not know how AmberTools works with acpype.py, I will go through it. Thanks very much for your suggestion, and still could you please help me with this error? Best wishes, Qinghua Liao -Sigue archivo adjunto- -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists-- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Acpype error
Dear Qinghua Liao, Could you give a little more information about your problem? How you ran the program? "./acpype -i "your_ligand_file.pdb" or what? Did you tested the installation? (At folder acpype/test) Does acpype properly installed? Does Ambertools properly installed? Best regards, Aldo ======= Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com = --- El lun 11-abr-11, fancy2012 escribió: De: fancy2012 Asunto: [gmx-users] Acpype error A: "gmx-users" Fecha: lunes, 11 de abril de 2011, 20:27 Hi GMX users, When I ran acpype.py on my computer, I got one error like this: File "./acpype.py", line 67, in from datetime import datetime ImportError: No module named datetime I use Python-2.6.6, I do not know how this error happen, could someone help me figure it out? Thanks very much in advance! -- Best wishes, Qinghua Liao Ph.D student of Tianjin University, China -Sigue archivo adjunto- -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists-- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] Umbrella sampling for protein-drug system
Dear gmx-users, I have following the umbrella sampling tutorial at http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html. I’m trying to use it for a drug-protein system. In the tutorial the group A moves away to group B. I would like to pull the drug to the protein binding-site (i.e., drug move closer to protein). How can I do that? Should I modified the md_pull.mdp file (from the tutorial) changing the value from pull_rate1 (0.01) to a negative value (i.e. -0.01)? or using pull_geometry = position and related code instead pull_geometry = distance? Thanks in advance, === Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com = -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] Protein-membrane system
Dear gmx-users, I completed a MD (10 ns) of my protein-membrane system. When I perform a visual inspection (VMD) of md_0_1.gro file I observed a few water molecules within the bilayer. In previous steps (e.g. equilibration) this was not observed. Could be expected such behavior? Best regards, == = Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com == === -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Help with B2AR within the POPC membrane
Dear Justin, You're right, I corrected the box vectors , and it works! Thanks, -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] Help with B2AR within the POPC membrane
Thanks for your answer. You're right in the procedure for the packing of the protein and lipids. However, after several iterations (~30) the lipids are packaged to form the bilayer and the protein is outside of it. I can send you a couple of pictures for a better explanation of my problem. Best regards, Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] Help with B2AR within the POPC membrane
Dear gmxusers, I need to perform molecular dynamics simulation of a B2AR within the POPC membrane. I have downloaded the 128b.pdb, popc.itp and lipid.itp files from Prof.Tieleman's group. My protein of interest is 343 residues. Also, I aligned the protein and membrane. I followed the Justin Lemkul tutorial for KALP-15. The result of inflate.gro is in agreement with the result showed in the tutorial (Visual inspection with VMD). However, the result of the first minimization shows that the protein and lipids are separated rather than starting to pack. I'm using gromacs-4.5.3. Can someone help me? my minim.mdp file: ; minim.mdp - used as input into grompp to generate em.tpr ; Parameters describing what to do, when to stop and what to save define = -DSTRONG_POSRES ; position restrain the protein integrator = steep ; Algorithm (steep = steepest descent minimization) emtol = 1000.0; Stop minimization when the maximum force < 1000.0 kJ/mol/nm emstep = 0.01 ; Energy step size nsteps = 5 ; Maximum number of (minimization) steps to perform ; Parameters describing how to find the neighbors of each atom and how to calculate the interactions nstlist = 1 ; Frequency to update the neighbor list and long range forces ns_type = grid ; Method to determine neighbor list (simple, grid) rlist = 1.2 ; Cut-off for making neighbor list (short range forces) coulombtype = PME ; Treatment of long range electrostatic interactions rcoulomb= 1.2 ; Short-range electrostatic cut-off rvdw= 1.2 ; Short-range Van der Waals cut-off pbc = xyz ; Periodic Boundary Conditions (yes/no) Best regards, Aldo Segura-Cabrera Laboratorio de Bioinformática Centro de Biotecnología Genómica Instituto Politécnico Nacional Blvd. Del Maestro esquina Elías Piña, 88710 Reynosa, Tamaulipas, México. (899)9243627 ext. 87747 e-mail: asegu...@ipn.mx; aldoseg...@gmail.com -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
