Thielges, Sabine wrote: >> Hi everyone, >> >> I am currently doing a simulation which involves a dopamine receptor >> placed in a POPC membrane and an agonist or antagonist in the active >> site. The ligand was placed by VS and is closed to what the biology >> gives. My problem is that the ligand get out of is normal position >> during the simulation. I know it is easier to move the ligand than the >> receptor but that is not the biological answer.
>If your system is not behaving in the biologically-dictated manner, I would >guess that whatever parameters you are using are unsuitable. Which force field >are you using, and where did you get the ligand parameters? How were they >validated? I am using the force field ffG53a6 for both, it was the one recommended by the membrane tutorial. the ligand parameters were created using the web site PRODRG which generates a drggmx.itp type that I have to manually modify since all the atoms types are not in the protein ff that I am using. Not the best but I didn't know which other ff would be appropriate for both receptor and ligand. >> I would like to know if there is a way to fix the ligand so that the >> receptor would be force to adapt around it and not the inverse. There >> is know Hbonds with specific amino acid is it possible to add this >> information in the run. > >You could implement distance restraints, but that would require merging the >moleculetypes, and again, if you're trying too hard to force something to >Happen, I would seriously question the accuracy of what you're doing. I have the same doubted, but I know for the receptor it self I had to do the same thing. I added position restraints that I gradually decreased from 1000 to 0 by doing few small MD and then I could do the real MD without any. My idea was to find a way to do the same thing with the drug nut I couldn't find any. How can I merge the 2 molecules since my ligand is not a protein and pdb2gmx doesn't work when I have it in my structure.pdb? >> I tried so far to use position restraint in my ligand.itp >> >> [ position_restraints ] >> ; i funct fcx fcy fcz >> 1 1 10000 10000 10000 >> 3 1 10000 10000 10000 >> 4 1 10000 10000 10000 >> 5 1 10000 10000 10000 >> 6 1 10000 10000 10000 >> 8 1 10000 10000 10000 >> 9 1 10000 10000 10000 >> 10 1 10000 10000 10000 >> 11 1 10000 10000 10000 >> 12 1 10000 10000 10000 >> 13 1 10000 10000 10000 >> >>But it didn't have any effect on the final MD simulation of 10 ns. At >>he end the ligand was completely out of the site. >> >Then you didn't actually apply position restraints. Did you use appropriate >define" statements in the .mdp file (if necessary)? I know that I don't because if I create a posre.itp for the drug like I do for the receptor and that I define it in my .mdp, I got a message error saying that I define atoms in the wrong molecule. Because the ligand is not the protein. Thanks again for your help. Sabine >-Justin > Could anyone help me? > > Thank you in advance > > Sabine > ======================================== Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justi _______________________________________________ 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/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/mailing_lists/users.php
