From Modeling to Medicinal Chemistry: Automatic Generation of Two-Dimensional Complex Diagrams

• Published in: ChemMedChem Vol. 2; no. 6; pp. 853 - 860
• Main Authors: Stierand, Katrin, Rarey, Matthias
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 11.06.2007; WILEY‐VCH Verlag
• Subjects: 2D visualization; 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; molecular interactions; Protein Interaction Mapping; protein-ligand complex; Software; structure diagrams; Structure-Activity Relationship
• ISSN: 1860-7179; 1860-7187; 1860-7187
• DOI: 10.1002/cmdc.200700010

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 ∼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 %. The visualization of protein ligand complexes is an important medium in the discussion of (structure‐based) drug design results between the modeler and the medicinal chemist. The new software tool poseview automatically generates 2D diagrams of given complexes, containing the ligand and the amino acids of the receptor, which are connected to the ligand by hydrogen bonds or hydrophobic contacts.