[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]

Re: the alignment problem

Hi Margot

Without wishing to sound egoistic, you might want to take a look at some
of my modelling articles.  The iterative approach to modelling is exactly
the one I take.  Basically, I make an initial alignment of my target with
one or more structures, based on fold recognition (often) adjusted using
common sense so that insertions and deletions are well accommodated.  I
then make a SET of models - 15 or 20, employing a large (4A) randomisation
in modeller.  In this way I try to explore lots of conformational
possibilities.  I then analyse the set with PROSA II (freely available)
which gives me 1) an overall score that can support or not the fold
recognition [there's the pG server too] and 2) profiles which highlight
problematic bits of the models.  I then look at the 'bad' bits to see if I
can imagine any alignment variants there that would produce better models
(more typically packed and better solvent exposure).  I then make new sets
of models with these new ideas and see if they're better than the original
set.  And so on, until I can't make any more improvements.

Assuming that PROSA II can distinguish between poorer and better models
(and there's cause for optimism - in the original paper it can pick up
threading errors in crystal structures) then the final model should be
better than the original.

I also do PROCHECK analysis, mainly towards the end.  I used to use
VERIFY_3D, but then we upgraded machines and I no longer have access.
Very frustratingly, this program seems unavailable.  There's a server for
individual structures but that's no use for people working with sets.

Best wishes


|                       Dr Daniel John Rigden                             |
| CENARGEN/EMBRAPA                 | e-mail:    |
| Parque Estacao Biologica         | http://www.cenargen.embrapa.br       |
| PqEB - Final - Av. W3 Norte      |  Phone:  +55 (61)448-4741            |
| 70770-900, Brasilia-D.F.-BRAZIL  |  Fax:    +55 (61)340-3658            |

On Thu, 4 Jul 2002, Margot Ernst wrote:

> Hi Modeller developers and friends,
> in Sanchez and Sali 1997 Curr Opin Struct Biol 7:206-214
> I read that a possible way to improve on homology modeling below 30 PID could
> be "iterative changes in the alignment during caluclation"
> My question is: Is this a great idea that has been realized already and I
>  just missed where and how, is it work in progress or has it been discarded
>  again due to technical problems?
> Could one, alternatively, if only one template is availble, use this template
> several times with different alignment variants (home-made version of
> modeling on several templates, so to speak) so that different homology
> derived restraints go into the same VTF, or is it, at present knowledge,
> better to go for ensembles of models and then try to construct one or more
> "best" consensus models?
> Any and all information and ideas are much appreciated!
> 	margot
> --
> Dr. Margot Ernst
> Abteilung Prof. Sieghart
> Institut f. Hirnforschung
> Spitalgasse 4
> A-1090 WIEN
> visit brainresearch: www.univie.ac.at/brainresearch