Computational approaches to drug design have always seemed to be an attractive proposition. The idea that drugs can be designed de novo has had a particular appeal and the ever-increasing availability and power of modern computers has made this possibility ever more mouth-watering. As more information on protein target structure becomes available, the prospect of such predicted potent small molecules becomes even more enticing. I would propose, however, that the value of in silico methods in drug design has moved on from this original premise to one where computational approaches now form complementary technologies to the wet lab. The articles included in this month’s newsletter were intended to show some examples of how computational approaches facilitate and expedite the discovery, development and licensing of new drugs. Using molecular similarity approaches, Willett et al. describe how being able to show differences in potential orphan drug candidates can be used to support licensing approaches and help with regulatory acceptance. The other two articles show how computation can accelerate the development of new drug molecules at the research bench showing how such technologies have been incorporated into standard drug discovery process maps, enhancing the overall drug discovery effort.    

The first article in this month’s offering is entitled: “Molecular similarity considerations in the licensing of orphan drugs”, by Pedro Franco, Nuria Porta, John D. Holliday and Peter Willett of the Information School, University of Sheffield, 211 Portobello Street, Sheffield S1 4DP, UK. In this article, the authors discuss the similarity of medicines in the context of orphan drug legislation. They point out that, as a result of the high cost involved in bringing new drugs to market, regulatory bodies need to provide incentives to promote the development of orphan drugs to treat serious conditions only affecting a small or very small number of patients. EU legislation, however, requires that they will only authorize drugs that can be demonstrated to be dissimilar from those already used to treat such diseases. This article outlines how 2D fingerprints can be used to calculate Tanimoto similarity between new and current drugs for particular diseases.

The second featured article is by Oscar Méndez-Lucio and José L. Medina-Franco of the Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico and is entitled: “The many roles of molecular complexity in drug discovery”. The authors discuss the concept of molecular complexity and those methods developed to assess it, however, they point out that, currently, there is no consensus as to how this should be done. This article critically evaluates the various quantitation methods and analyses, using reference compound databases the various issues associated with the individual methods and how these may be circumvented.

Finally, is the article “Computational functional group mapping for drug discovery” from Olgun Guvench from SilcsBio, LLC, 8 Market Street, Suite 300, Baltimore, MD 21202, USA. The article describes computational functional group mapping and how it is being incorporated within current experimental and in silico drug discovery projects. The method can generate 3D maps of functional groups of potential drug molecules and their affinity for the required target. These maps can help the medicinal chemist rapidly to design molecules with high affinity that are relatively easy to synthesize. The author outlines recent advances in the topic and emphasizes the unique information that can be derived from the approach and how it offers great potential for structure-based design of novel ligands. 

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents.