Computer Aided Drug Design

Partnering computer-aided techniques with high-throughput screening seen as the new gold standard in drug design.

Computer-aided virtual screening (VR) answers the question of how scientists working on new drug design can rapidly reduce a huge library of compounds down to a manageable size. In silico screens are faster and less expensive than high-throughput screens. “Because HTS data is not trustworthy for building predictive models, scientists are instead using the high-quality data generated by biologists within project campaigns to design models,” according to Frank Brown, VP and CSO of Accelrys. “They then rely on virtual screening to identify well-defined compound sets, often a focused library, which can be used to guide the preparation of HTS plates to screen against a particular target class.”

While VR technology is usually viewed as a way to generate a prioritized list of targets in order to eliminate the need for as many high-throughput screens, “It has also been shown that the ‘hits’ from VS [virtual screening] when compared to HTS [high-throughput screening] are often diverse and independent, suggesting that VS and HTS might be considered complementary methods,” according to R. Brenk, et al. in The Journal Bimolecular Screening. The pairing of these two technologies should act as an accelerator for the drug development industry.

Best-in-Class Computer Aided Drug Design Providers:

• Has access to enough computing power to handle several independent variables and extremely large matrices
• Utilizes advanced multivariate analysis tools like PCA, PLS, CPCA
• Willing to educate customer’s staff about capabilities and limitations of CADD

Top Considerations Before Selecting Computer Aided Drug Design Provider:

Don’t be fooled by providers that guarantee a large number of hits. Success of a virtual screen is defined by the number of interesting new scaffolds found rather than by the total number of hits, since this may include many scaffolds that have been previously indentified.

Key Producers:

1. Computer-aided drug design is one of the tools employed by WuXi AppTec’s Integrated R&D Services which the company reports as being a “broad and integrated portfolio of laboratory and manufacturing services throughout the drug and medical device R&D process.” Other services offered by this global enterprise are Pharmaceutical, Biologics, Combination, Medical Device and Toxicology Services. WuXi AppTec was established in 2000 and has operations in China and the United States.

2. Argenta Discovery Limited's computer-aided drug design group works closely with its medicinal chemists to enable them to visualize the modeling results. Its specialty is integrated small molecule drug discovery services.  It can take over any or all aspects of a customer's drug discovery program, including hit identification, hit-to-lead and lead optimization. Argenta’s scientists have experience with all small molecule target classes such as GPCRs, kinases, proteases and other enzyme families, nuclear receptors, integrins and ion channels. Argenta is a UK-based fee-for-service contract research business that also offers risk-sharing deals. Argenta spun off from Aventis’ UK Research Centre in 2000 and merged with Etiologics Limited in 2004.

3. Synergix Ltd's Molecular Conceptor Learning Series is an interactive, multi-media e-learning course that covers knowledge of medicinal chemistry, drug design, cheminformatics, structural bioinformatics and molecular modeling, including computer assisted drug design. Each module, which uses interactive 3D technology, practical examples and case studies, covers a drug discovery-related topic, beginning with basic principles. The company reports that "Molecular Conceptor is currently used by more than 450 academic institutions and pharmaceutical companies worldwide." Synergix was founded in 1996 to develop educational resources for drug design, molecular modeling, cheminformatics and medicinal chemistry.

4. Novartis' Computer-Assisted Drug Discovery group in Cambridge, MA is an integral part of the Cambridge Medicinal Chemistry group, but is fully interconnected with Novartis' Global CADD community. Novartis is a multinational pharmaceutical company that is involved in publicly funded collaborative research projects as well as its internal drug research and development program. Novartis reports that in 2009 they "invested USD 7.5 billion in research and development. This is one of the highest figures in the industry relative to sales (17%)." This global company, which operates in 140 countries, was created in 1996 through the merger of Ciba-Geigy and Sandoz. Headquarters are in Basel, Switzerland.

Computer Aided Drug Design
Definition: Computer-assisted drug design uses computer software to discover new drugs. Virtual screening (VS) involves docking 3-D models of candidate ligands into a 3-D model of a protein target and then applying a scoring function to estimate the likelihood that the ligand will bind to the protein with high affinity.