From chemistry-request -8 at 8- ccl.net Mon Sep 6 07:12:39 2004 Received: from smtp.dmbr.UGent.be (dmbr242.fvms.ugent.be [157.193.189.5]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i86CCbaG008201 for ; Mon, 6 Sep 2004 07:12:38 -0500 Received: from [157.193.200.22] (dmbr015.fvms.ugent.be [157.193.200.22]) by smtp.dmbr.UGent.be (Postfix) with ESMTP id 93E758003C; Mon, 6 Sep 2004 14:22:07 +0200 (CEST) Message-ID: <413C5672.5070701)at(dmbr.ugent.be> Date: Mon, 06 Sep 2004 14:22:10 +0200 From: Dominique Vlieghe User-Agent: Mozilla/5.0 (X11; U; Linux i686; en-US; rv:1.7.2) Gecko/20040803 X-Accept-Language: en-us, en MIME-Version: 1.0 To: "Dr. Csaba Hetenyi" Cc: chemistry)at(ccl.net Subject: Re: CCL:predict 3D structure from sequence (fwd) References: In-Reply-To: Content-Type: text/plain; charset=ISO-8859-1; format=flowed Content-Transfer-Encoding: 7bit X-Spam-Status: No, hits=0.9 required=7.5 tests=MY_BAD_DOT autolearn=no version=2.61 X-Spam-Checker-Version: SpamAssassin 2.61 (1.212.2.1-2003-12-09-exp) on servernd.ccl.net Dr. Csaba Hetenyi wrote: >>The first one called Camparative Protein Modeling, which requires a 3d >>structure of a protein, which has >30% sequence Similarity comparing to >>target. It's pretty reliable. The second approach has lower success >>rate.. >> >> > >I'd rather not say "it is pretty reliable". In my view, sequence >similarity (30 % or above) is not a sufficient only a necessary >requirement of possible homology modeling (HM). >A "nice" example of failure of HM was recently mentioned in Williams et >al. Science 305 (2004) 683-686. E.g. 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). > > Sadly, I must say from personal experience I agree with you, but the problem remains that one often has to homology model a given receptor, because a xray/nmr structure is lacking. We as end-users of docking algorithms cannot wait for the experimental structures, because it is almost always the case that the crystal structure is one of the last pieces of information that is available (i.e. an experimental validation of a certain protein-ligand interaction has been published before the structures are known). Does this mean that computational docking is not useful in a practical sense? And what do you think about high-throughput homology modeling set-ups (ModBase,...)? Regards Dominique >Sorry, if i was too negative concerning HM. >Best wishes, >Csaba > > > > >-= This is automatically added to each message by the mailing script =- >To send e-mail to subscribers of CCL put the string CCL: on your Subject: line >and send your message to: CHEMISTRY)at(ccl.net > >Send your subscription/unsubscription requests to: CHEMISTRY-REQUEST)at(ccl.net >HOME Page: http://www.ccl.net | Jobs Page: http://www.ccl.net/jobs > >If your mail is bouncing from CCL.NET domain send it to the maintainer: >Jan Labanowski, jlabanow)at(nd.edu (read about it on CCL Home Page) >-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ > > > > > > > -- ------------------------------------------------------------------------ Save the Hubble petition: http://www.savethehubble.org ------------------------------------------------------------------------ Dominique Vlieghe, Ph.D., Bioinformatics Core, Department for Molecular Biomedical Research (DMBR) VIB - Ghent University Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium ------------------------------------------------------------------------ email: dominique.vlieghe)at(dmbr.ugent.be tel: +32-(0)9-33-13.693 www: http://www.dmbr.ugent.be/ fax: +32-(0)9-33-13.609 ------------------------------------------------------------------------