From modeling to medicinal chemistry: automatic generation of two-dimensional complex diagrams

ChemMedChem. 2007 Jun;2(6):853-60. doi: 10.1002/cmdc.200700010.

Abstract

As a result of the increasing application of structure-based drug design, the visualization of protein-ligand complexes has become an important feature in medicinal chemistry. The large number of experimentally resolved complex structures and the further development of computer-aided methods like docking or de novo design establishes new possibilities in this field. During lead finding and optimization, a manual investigation of many complexes and their interaction patterns is typically performed. We present an algorithm that automatically generates 2D-protein-ligand diagrams as a possible solution for a transparent visualization of the contact partners in a complex and as a support for scientists in the evaluation of structure-based design results. Running the software on representative test data sets, it generates collision free layouts for approximately 76% of the cases in the range of tenths of a second per complex. The success rate for complexes with ligands which have a molecular weight <500 Da is 87%.

MeSH terms

  • Algorithms
  • Chemistry, Pharmaceutical / methods
  • Chymotrypsin / chemistry
  • Chymotrypsin / metabolism
  • Computer Simulation*
  • Drug Design*
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / metabolism
  • Flavodoxin / chemistry
  • Flavodoxin / metabolism
  • HIV Protease / chemistry
  • HIV Protease / metabolism
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Metals / chemistry
  • Metals / metabolism
  • Models, Molecular*
  • Protein Interaction Mapping
  • Software
  • Structure-Activity Relationship

Substances

  • Estrogen Receptor alpha
  • Flavodoxin
  • Ligands
  • Metals
  • Chymotrypsin
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1