JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION受体与信号杂志.pdfVIP

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION Vol. 23, No. 4, pp. 361–371, 2003 MINIREVIEW Tautomerism in Computer-Aided Drug Design Pavel Pospisil,* Patrick Ballmer, Leonardo Scapozza, and Gerd Folkers Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zu¨rich, Zu¨rich, Switzerland ABSTRACT 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. Key Words: Tautomer; Chemical database; Tautomer binding site; Virtual screening. 1. INTRODUCTION Numerous collections of chemical compounds are stored in electronic form and various techniques are used to filter out compounds having the so-called ‘‘drug-like’’ properties (1,2). Using automatized molecular docking programs, small molecules are *Correspondence: Pavel Pospisil, Department of Chemistry and Applied Biosciences, Swiss Federal Ins