Subject: Re: CCL:predict 3D structure from sequence

From: jerome{at}scs.uiuc.edu
Date: Mon, 06 Sep 2004 11:02:26 -0500

>> A "nice" example of failure of HM was recently mentioned in Williams et
>> al. (...) CYPs are "excellent" examples of
>> proteins not appropriate for HM. Extensive, uncontrolled use of HM (or -
>> horribile dictu - HM and
>> consecutive docking on a HMed target contributes to rising (and - in this case - right) scepticism of experimental guys against modeling (against us).

The definitive aspect of this statement sounds too ideological to me .. 
There *are* exemples of successsful HM/HTS using CYPs templates..
By sucessfull I mean either identification, confirmed experimentaly,  of 
ligands through virtual screening or QSAR-like experimental/theoretical 
agreement on ligand/protein binding energies/Kd ... 

I agree that  *uncontrolled* HM/docking is a plague, by I want to stress 
that the oposite is also true: successful HM/docking - in particular in the 
P450 world, contributes (to paraphrase) to "rising (and - in this case - 
right) confidence of experimental guys with modeling." As always when theory 
is involved, experiental confirmation is the key ...same old same old.. 

 ----------------------------------------------------------
Jerome Baudry, Ph.D.       Senior Research Scientist, VizLab Manager.
School of Chemical Sciences    University of Illinois at Urbana-Champaign
505 S. Mathews Ave.; Box 2.1; Urbana, IL, 61801
Phone: (1) (217) 244 3210; Fax: (1) (217) 333 3120;    e-mail:
jerome{at}scs.uiuc.edu

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From: "Dr. Csaba Hetenyi" <csaba{at}ovrisc.mdche.u-szeged.hu>
Date: Mon, 6 Sep 2004 18:18:20 +0200 (CEST)

> The definitive aspect of this statement sounds too ideological to me .. 

Indeed, it was a bit ideological. In my view, the problem of homology
modeling is very similar to e.g. genetic modification of
plants. We do not know exactly what comes out of it... We cannot
analyze/validate all of the results. Can we use it?
Best wishes,
Csaba