|
|
| The View From Here Enjoy! David E. Clark Dr David E. Clark is Director of Computer-aided Drug Design (CADD) and Information Services at Argenta Discovery, of which he was a founding scientific team member in August 2000. David began his career working for Proteus Molecular Design for three years where he was involved in developing software for de novo ligand design and protein-ligand docking. He then spent four years working in the CADD group of Aventis/Rhone-Poulenc Rorer before joining Argenta. In 2003, David was the recipient of the Corwin Hansch award, which is presented annually by the QSAR and Modelling Society. |
Virtual screening (VS) is the computational counterpart of biochemical high-throughput screening (HTS). Using specialised computer programs, large numbers of chemical compounds are assessed for their likelihood of exhibiting a particular biological activity, either by “docking” them into the active site of a protein (structure-based VS) or by comparing them to known active compounds (ligand-based VS). Over the last decade, virtual screening has become a widely applied technique for the discovery of novel lead compounds and many success stories have been reported in the scientific literature. However, there are still challenges to be overcome including the treatment of protein flexibility, the development of scoring functions able to rank order compounds correctly in terms of their biochemical activities and the analysis of the voluminous data generated during VS. Furthermore, best practice is still being established as experience is gained during the practical application of the methods. For instance, a key realisation has been that, even when an X-ray structure of the biochemical target of interest is available, ligand-based VS should still be applied in order to maximise the likelihood of success. Additionally, the criterion for measuring the success of VS campaigns is now focused much more on the number of hit series discovered, rather than just the hit-rate, which can be heavily biased by the presence of analogue series. Nevertheless, in the hands of experienced practitioners, VS provides a powerful, rapid and cost-effective means of accelerating drug discovery programmes. In the future, ever-increasing computer power coupled with more sophisticated software should ensure a growing role for VS in pharmaceutical research.