[gmx-users] pca-based MD

[James Starlight]

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 <tevang3 at gmail.com>:
> 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 <jmsstarlight at gmail.com> 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
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>
>
>
> --
>
> ======================================================================
>
> Thomas Evangelidis
>
> PhD student
> University of Athens
> Faculty of Pharmacy
> Department of Pharmaceutical Chemistry
> Panepistimioupoli-Zografou
> 157 71 Athens
> GREECE
>
> email: tevang at pharm.uoa.gr
>
>           tevang3 at gmail.com
>
>
> website: https://sites.google.com/site/thomasevangelidishomepage/
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