Tautomerism in computer-aided drug design.
Tautomers are often disregarded in computer-aided molecular modeling applications. Little is known about the different tautomeric states of a molecule and they are rarely registered in chemical databases. Tautomeric forms of a molecule differ in shape, functional groups, surface, and hydrogen-bonding pattern. Calculation of physical-chemical properties and molecular descriptors differ from one tautomeric state to the other as it is demonstrated with an example of the log P calculation, similarity index, and the complementarity pattern to the targeted protein. Considering tautomery in ligand-protein interactions therefore has a significant impact on the prediction of the ligand binding using various docking techniques. This article points on hitherto unaddressed issue of tautomerism in computer-aided drug design.
Pospisil
Pavel
P
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland. pavel.pospisil@pharma.ethz.ch
Ballmer
Patrick
P
Scapozza
Leonardo
L
Folkers
Gerd
G
D001665:Binding Sites; D003198:Computer Simulation; D019992:Databases as Topic; D015195:Drug Design; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D012984:Software
D008024:Ligands