Dear Mark, Thanks and you are right, that when a docked complex (protein + ligand) is simulated, the favorable ligand binding poses can be predicted using MD (longer runs). What I am trying to do here presently is not to simulate a docked complex, but to generate a modelled protein lowest energy configuration (P.E. surface exploration) using MD and further use this configuration for the flexible docking, and you are right as I think MD follows the law of conservation of energy as the P.E decreases the K.E increases or vice versa for a configuration at an instance, as we are exploring the P.E surface by changing the coordinates very effectively using M.D, i want use the configuration (coordinates) with the lowest P.E produced from MD and further minimize it (as i dont know whether the configuration obtained after gromacs MD can go further into a local/global minima by minimization) so that can be the input for flexible docking.
Thanks, Ram On Thu, Oct 22, 2009 at 4:59 PM, Mark Abraham <[email protected]> wrote: > ram bio wrote: >> >> Dear Mark, >> >> You mean that I should consider a configuration with the lowest total >> energy for docking studies..Please clarify and suggest me. > > If you read your docking program's documentation, they are using their > "energy" as a some kind of approximation to a free energy of ligand binding > (or some such). There could be all kinds of ad-hoc contributions that they > may have been able to demonstrate worked usefully enough on their test set > to be worth including. > > There's no reason to assume an MD potential "energy" (which itself is a > combination of more-or-less ad-hoc parameters) would correlate with the > above, since the MD potential wasn't parameterized to do that. It'd be > especially flawed to suppose that the fact that energy in MD is distributed > over PE and KE is immaterial. Low PE just means high KE. > > To identify favourable ligand-binding orientations with MD requires an > immense amount of sampling. In effect, you need to do enough MD to allow the > ligand to come in and out of the site many times in many different ways and > to compare the relative frequency so that you can also estimate the entropy > component of the free energy change associated with various binding modes > relative to each other. Even for implicit solvent calculation models, the > history of computing probably doesn't provide enough cycles to do this with > decent accuracy. Hence, docking. > > MD can be useful in more limited "docking" studies - a highly unfavourable > binding conformation will fly apart rapidly - but you'd hope the docking > force field could tell you about those cases! > > It sounds like you should really be doing some more background reading about > docking and MD, to better understand the methods you're using. > > Mark > >> On Thu, Oct 22, 2009 at 3:56 AM, Mark Abraham <[email protected]> >> wrote: >>> >>> ram bio wrote: >>>> >>>> Dear Justin, >>>> >>>> Thanks for the suggestion and advice. >>>> As i have used a modelled protein and want to obtain the lowest energy >>>> configuration of the protein by doing dynamics, >>> >>> That's all very well, but what will that give you other than a set where >>> the >>> partition of total energy into potential and kinetic was skewed one way? >>> >>> Mark >>> _______________________________________________ >>> gmx-users mailing list [email protected] >>> 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 [email protected]. >>> Can't post? Read http://www.gromacs.org/mailing_lists/users.php >>> >> _______________________________________________ >> gmx-users mailing list [email protected] >> 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 [email protected]. >> Can't post? Read http://www.gromacs.org/mailing_lists/users.php >> > _______________________________________________ > gmx-users mailing list [email protected] > 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 [email protected]. > Can't post? Read http://www.gromacs.org/mailing_lists/users.php > _______________________________________________ gmx-users mailing list [email protected] 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 [email protected]. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
