From chemistry-request(+ at +)ccl.net Wed Mar 3 07:24:23 2004 Received: from collapsed.wormhole.hu (collapsed.wormhole.hu [195.70.35.130]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i23COMd4029057 for ; Wed, 3 Mar 2004 07:24:22 -0500 Received: from szilva (helo=localhost) by collapsed.wormhole.hu with local-esmtp (Exim 3.36 #1 (Debian)) id 1AyVRf-0000es-00 for ; Wed, 03 Mar 2004 13:25:51 +0100 Date: Wed, 3 Mar 2004 13:25:51 +0100 (CET) From: szilva-.at.-computer.org X-X-Sender: szilva-.at.-collapsed.wormhole.hu To: CCL Subject: Re: CCL:Docking software vithout validation In-Reply-To: Message-ID: References: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Sender: Szilveszter JUHOS Dear All, I know very well that validating a docking software is rather time consuming and needs some experience. Note I spent some time (years) in a group with validating and developing a docking software that is used in-house at a durg-discovery company. Docking softwares originally were developed to restore Xtal ligand structures quickly and virtual screening were not always in mind at the birth of these tools. Luckily, they can be used for hit-id as well, that is a very handy "by-product". Though validation is expensive but necessary: as it is unacceptable from a car-manufacturer to leave its products validation for the customers, it is true for all other products - for software as well. Choice is a result of comparison: with validation data I can choose between A_dock and B_dock. I do not want to impose a compulsory validation set on any developer but sticking to a cleared set that is used by other programs also makes the choice easier for the customer. The source of these programs likely will not be freely available for quite a while and it is understandable. Docking is still a new technology and the competition is already strong. As for me the main validation points would be (and it is about the scheduling the validation also): i) reproducing RMSD on a large target set ii) checking selectivity (ie with cross-docking matrix) iii) proving docking can select active compounds from a random library iv) providing tools for post-processing (discarding false positives, opportunistic binders) One can argue the last step is not the docking software's task but I want to emphasize my point of view is that such a "docking platform" has a role to select putative leads from a large virtual library. As for this step iv) is required because the crude run-results are heavily polluted with false positives. Usually people are expecting docking to reproduce not only the exact X-ray conformation of the ligand but the free energy (dG) values as well. My opinion is that this is not the task of docking: the dG values in the literature are quite unreliable and there are other problems with the scoring functions also. Cheers: Szilva PS: sorry not to include all the mails I responded to, but this lengthy email would be even longer.