Benefits of structural genomics for drug discovery research

Marek Grabowski, Maksymilian Chruszcz, Matthew D. Zimmerman, Olga Kirillova, Wladek Minor

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


While three dimensional structures have long been used to search for new drug targets, only a fraction of new drugs coming to the market has been developed with the use of a structure-based drug discovery approach. However, the recent years have brought not only an avalanche of new macromolecular structures, but also significant advances in the protein structure determination methodology only now making their way into structure-based drug discovery. In this paper, we review recent developments resulting from the Structural Genomics (SG) programs, focusing on the methods and results most likely to improve our understanding of the molecular foundation of human diseases. SG programs have been around for almost a decade, and in that time, have contributed a significant part of the structural coverage of both the genomes of pathogens causing infectious diseases and structurally uncharacterized biological processes in general. Perhaps most importantly, SG programs have developed new methodology at all steps of the structure determination process, not only to determine new structures highly efficiently, but also to screen protein/ligand interactions. We describe the methodologies, experience and technologies developed by SG, which range from improvements to cloning protocols to improved procedures for crystallographic structure solution that may be applied in "traditional" structural biology laboratories particularly those performing drug discovery. We also discuss the conditions that must be met to convert the present high-throughput structure determination pipeline into a high-output structure-based drug discovery system.

Original languageEnglish
Pages (from-to)459-474
Number of pages16
JournalInfectious Disorders - Drug Targets
Issue number5
StatePublished - 2009
Externally publishedYes


  • Drug discovery
  • Infectious disease
  • Protein-small molecule complexes
  • Structural genomics
  • Structure determination


Dive into the research topics of 'Benefits of structural genomics for drug discovery research'. Together they form a unique fingerprint.

Cite this