VMD-L Mailing List

From: L. Michel Espinoza-Fonseca (mef_at_ddt.biochem.umn.edu)
Date: Sat Sep 29 2007 - 14:05:01 CDT

Hi Kalyan

> Iam very new to VMD, am working on Transmembrane protein (GPCR), i learnt
> that molecular interactions of transmembrane protein can better be
> understood by building a membrane, i.e simulations and docking results are
> more relaible when performed with membrane bound transmembrane protein.
>
> my doubt is-
>
> 1. is it true that membrane building (for TM protein) would make a
> difference in the docking studies.

It depends on many factors. If you know that your ligand binds to the
orthosteric site, usually a good starting template of the receptor
should work well only if you want to find the orientation and internal
conformation of that ligand in the binding site. There are other
cases, where certain ligands bind to unknown allosteric sites in the
surface of either the cytoplasmic or the extracellular regions of the
protein, then the problem becomes a little bit trickier and you might
need a membrane in your system. If you happen to have an amphipathic
ligand that is potentially an allosteric binder, but also interacts
with the membrane, then you'll definitively need a membrane included
in your model.

In summary, if you simply want to obtain a 3-D model of the
ligand-receptor complex, then I'd suggest you to build a GOOD
template, apply some of the state-of-art methods available to optimize
the packing of the helices and the Chi angles of the side-chains
(i.e., by using rotamer libraries). In this case you don't need to
build a membrane-protein system. If you want to get information of the
dynamics of the receptor + your ligand, then I'd recommend you to go
for the explicit membrane simulations. In either case, the crucial
step here is to obtain a GOOD INITIAL STRUCTURE of the receptor. The
quality of your results will strongly depend on this.

> 2. If yes how to build membrane using VMD

This, of course, depends on what you have decided considering the
previous paragraphs.

Cheers,
Michel
>
> please help me in undersanding the same.
>
> Thank you in advance,
>
> Kalyan chaitanya.P
>