Structural biology and drug discovery

Curr Pharm Des. 2006;12(17):2087-97. doi: 10.2174/138161206777585201.


In the past few years macromolecular crystallography has become a standard technique used by many pharmaceutical and biotechnology companies. This methodology offers details of protein-ligand interactions at levels of resolution virtually unmatched by any other technique, and this approach holds the promise of novel, more effective, safer and cheaper drugs. Although crystallography remains a laborious and rather expensive technique, remarkable advances in structure determination and structure based drug design (SBDD) have been made in recent years. This process has been aided by recent technological innovations such as high-throughput crystallization, high performance synchrotron beamlines, and new methods in structural bioinformatics and computational chemistry prompted by the structural genomics effort. As a consequence of the increased availability of structural data, the use of structure-based information has expanded from simple protein-ligand interaction analysis to include other aspects of the drug discovery process like target selection and initial lead discovery that used to be almost the exclusive property of biology and chemistry. This review will cover recent examples to illustrate how macromolecular crystallography has evolved and how structural information is now being used in the different stages of the drug discovery process. Advantages and shortcomings of the methodology will also be discussed.

Publication types

  • Review

MeSH terms

  • Combinatorial Chemistry Techniques / trends*
  • Computer Simulation
  • Crystallography, X-Ray
  • Databases, Genetic
  • Drug Design*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Mutagenesis
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Structural Homology, Protein
  • Structure-Activity Relationship


  • Ligands
  • Pharmaceutical Preparations
  • Proteins