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An Automatic Virtual Screening System

We are pleased to present the following seminar with audio on the eCheminfo Hub which is available for viewing and discussion.  Please signup/log into echeminfo.com to view it.  This seminar is available and free to all site visitors.

An Automatic Virtual Screening System, John Irwin and Brian K. Shoichet, UCSF

Notwithstanding well-known algorithmic weaknesses, molecular docking screens have had important successes in recent years, and are now the most practical technique to leverage structure for ligand discovery. Unfortunately, barriers to entry have largely restricted the techniques to experts and their collaborators. Docking databases are expensive to acquire, require considerable manipulation, and the software is byzantine. Many pitfalls await the unwary docker, such as the preparation of the protein binding site and the choice of dozens of parameters. This has diminished the impact of the technique and limited the sorts of problems to which it can be applied. To address this situation we are building tools and databases that will bring docking to a broad audience, in the spirit of BLAST, and allow its application to new questions. This talk will describe the development of and experience with an early prototype of an automated web-based docking system and its components. We will illustrate some of the strengths and weaknesses of this approach against targets of current or recent therapeutic interest.

Barry Hardy
Douglas Connect
Tel: +41 61 851 0170

eCheminfo Community of Practice
echeminfo.com

Virtual screening and computer-based design of drug candidates against unknown targets

If one has solved the structure of a known drug target, computational modelling and design approaches can be applied to ligand design to help guide the design of potential drug candidates which can then be tested in the laboratory.  However, if one does not know the target structure the problem is more intractible.  One expensive approach is to throw many compounds against the target in massive screening and combinatorial cehmistry experiments in the lab and then almost blindly sift out candidates with the most promising affinities.  Apart from the significant cost of such efforts, one is literally searching for a needle in a haystack of trillions of billions of chemical possibilities.  David Lloyd describes approaches developed by De Novo Pharmaceuticals (www.denovopharma.com) which can be used to tackle this situation in the computer laboratory whereby 2.5 million compounds can be screened per day on an 80-node computer farm.