Where oh where is a 5-HT2A Model?

[SNR]

I wish to model the 5-HT2A receptor (along with a ton of other GPCR's), and I've already seen a few papers with it modeled. Yet I can't find a model that I can use! Can anyone help me out here?

 

[Erny]

Vignir Ísberg, Thomas Balle, Tommy Sander, Flemming Steen Jørgensen, and David E. Gloriam
G Protein- and Agonist-Bound Serotonin 5-HT2A Receptor Model Activated by Steered Molecular Dynamics Simulations
J. Chem. Inf. Model., 2011, Article ASAP.
DOI: 10.1021/ci100402f

Will this one suite you? http://depositfiles.com/files/v7jks19yh

 

[nuke]

There is no X-ray crystal structure, so no real valid model. There are some published guesses, though.

 

[pharmakos]

who has an xray crystal machine and why haven't they modeled the 5ht2a receptor yet?

 

[nuke]

who has an xray crystal machine and why haven't they modeled the 5ht2a receptor yet?

You need a synchrotron and a lot of other hardware. Additionally, the receptor itself must crystallize, which is not an easy feat. The multimers of 5HT2 receptors are like barrels whose rounded sides are covered with hydrophobic residues, which make it great for embedding in membranes but awful for making crystals.

 

[skillet]

who has an xray crystal machine and why haven't they modeled the 5ht2a receptor yet?

hehe check out what it took to get a crystal of the active beta-2 adrenoreceptor - link

in summary:

These binding data suggest that Nb80 stabilizes a conformation in WT β2AR that is very similar to that stabilized by Gs, such that the energetic coupling of agonist and Gs binding is faithfully mimicked by Nb80... While we cannot study G protein coupling in β2AR-T4L due to steric hindrance by T4L, the results show that T4L does not prevent binding of Nb80. (Nb80 mimics Gs binding and helps activate the receptor)

To further stabilize the active state of the β2AR, we screened over 50 commercial and proprietary β2AR ligands.

Efforts to crystallize β2AR-Fab complex and β2AR-T4L bound to BI-167107 (best agonist from screening) and other agonists failed to produce crystals of sufficient quality for structure determination. We therefore attempted to crystallize BI-167107 bound to β2AR and β2AR-T4L in complex with Nb80. While crystals of both complexes were obtained in lipid bicelles and lipidic cubic phase (LCP), high-resolution diffraction was only obtained from crystals of β2AR-T4L-Nb80 grown in LCP. These crystals grew at pH 8.0 in 39–44% PEG400, 100 mM Tris, 4 % DMSO, and 1% 1,2,3-heptanetriol.

A merged data set at 3.5 Å was obtained from 23 crystals

Probably screened thousands of crystallisation conditions, after all the prep work. And I guess you have to x-ray any crystals you get to see how good they are, and most of them are probably crap.

 

[SNR]

Vignir Ísberg, Thomas Balle, Tommy Sander, Flemming Steen Jørgensen, and David E. Gloriam
G Protein- and Agonist-Bound Serotonin 5-HT2A Receptor Model Activated by Steered Molecular Dynamics Simulations
J. Chem. Inf. Model., 2011, Article ASAP.
DOI: 10.1021/ci100402f

Will this one suite you? http://depositfiles.com/files/v7jks19yh

Yes it will! Experimental models are what I was looking for! Thanks so much.

 

[pharmakos]

Probably screened thousands of crystallisation conditions, after all the prep work. And I guess you have to x-ray any crystals you get to see how good they are, and most of them are probably crap.

so they make like thousands and thousands of crystals and look at each one until they find one that crystallized in the right form?

science like that would annoy me so much lol bless you any of you guys that actually have the patience to do something like that.

 

[skillet]

Most of the conditions probably don't give crystals, I don't know how many you'd typically get. But you'd have to look at the ones you do get to see which conditions gave the best crystals.

Yeah hopefully they have robots that can do some of the work, it would suck to do it all by hand!

I don't know if anyone has tried with any of the 5-HT receptors, I guess they must have?