Hi, Thomas! I'd like to ask you some addition questions about FMA. As I understood from the FMA page that technique is something like integrator of principal components (merge some PCs with identical functional motion seen in the X-ray structures for instance) calculated from g_covar. So FMA is also Hessia-based method (assuming that cov.matrix is inverse of the Hessian) for studing functional motion in protein isnt?
Some technical questions: Have you tried to extract functional modes from X-ray data set (not from of unbiased md as in case of EDS) of your kinase for further md-guiding ( e.g by means of EDS) of that protein along some functional modes? Have you tried use it with the gromacs 4.5 ? I've found that only for older gromacs releases. Does it possible to visualise motion along FM in vmd or mol script ? Thanks for help James 2012/9/23 Thomas Evangelidis <[email protected]>: > I presume you are referring to Essential Dynamics Sampling, described in > section 3.14 of the manual (v4.5.4). There is also a great tool that finds > the few PCs that are maximally correlated to a functional quantity (e.g. > the volume of the active site). The technique is coined Functional Mode > Analysis (FMA) and you can find more information at: > > http://xray.bmc.uu.se/~jochen/fma.html > > I have used FMA and worked pretty well in my case. I am wondering if anyone > thought of using that technique to find the PCs that are maximally > correlated to a functional quantity and then perform Essential Dynamics > sampling on these PCs to explore the conformational space that affects the > most that functional quantity. > > I.e. I am studying a kinase in the wt and mutant form. Although the > mutation is not near the active site there is a lot of discussion in the > literature about the effect of the mutation on the opening of the catalytic > cleft. Some people claim that one possible explanation of the over-activity > of the mutant is the greater opening of the active site, which facilitates > substrate binding and thus leads to enhanced reaction turn-over. In order > to test this hypothesis with unbiased MD one would need tremendous computer > resources and a lot of time (the kinase is gigantic). On the other hand one > could run short simulations of the wt and mutant, do FMA to find the 10-20 > PCs that are maximally correlated to the volume of the active site, and > then perform Essential Dynamics Sampling on these PCs to explore the > conformational space that is highly correlated to the volume of the active > site. After that, one could safely claim that the Hypothesis was true or > false. > > I would be interested to read your comments on this. > > Thomas > > > On 23 September 2012 11:19, James Starlight <[email protected]> wrote: > >> Dear Gromacs Users! >> >> >> There are many publications about implementation of the pca-based MD >> simulations for the investigation of the functional-relevant motions. >> In that cases the eigenvectors are extracted from the relatively short >> MD simulation of the investigated protein and than the biassed MD >> simulation is started along chosen principal component which used as >> the reaction coordinate. >> >> I'd like to know more about implementation of that technique in >> Gromacs. E.g if I've performed some PCA and extracted eigenvectors how >> I can run further simulation along one of the chosen PC ? >> >> Thanks for help >> James >> -- >> gmx-users mailing list [email protected] >> 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 [email protected]. >> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists >> > > > > -- > > ====================================================================== > > Thomas Evangelidis > > PhD student > University of Athens > Faculty of Pharmacy > Department of Pharmaceutical Chemistry > Panepistimioupoli-Zografou > 157 71 Athens > GREECE > > email: [email protected] > > [email protected] > > > website: https://sites.google.com/site/thomasevangelidishomepage/ > -- > gmx-users mailing list [email protected] > 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 [email protected]. > * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- gmx-users mailing list [email protected] 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 [email protected]. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
