From modeling to medicinal chemistry: automatic generation of two-dimensional complex diagrams.
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%.
Stierand
Katrin
K
Center for Bioinformatics, University of Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany.
Rarey
Matthias
M
D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002918:Chymotrypsin / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism; D005418:Flavodoxin / Q000737:chemistry / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008670:Metals / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D025941:Protein Interaction Mapping; D012984:Software; D013329:Structure-Activity Relationship
D047628:Estrogen Receptor alpha; D005418:Flavodoxin; D008024:Ligands; D008670:Metals; D002918:Chymotrypsin; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1