Application of EMBM to Structure‐Based Design of Warheads for Protease Inhibitors. Issue 1 (24th October 2013)

• Record Type: Journal Article
• Authors: Traube, Tamar; Shokhen, Michael; Albeck, Amnon
• Is Part Of: Molecular informatics. Volume 33:Issue 1(2014:Jan.)
• Page Start: 36
• Page End: 42
• Publication Date: 2013-10-24
• Subjects: Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.201300099
• Languages: English
• ISSNs: 1868-1743

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Most CADD tools handle non‐covalent enzyme inhibitors, despite the growing interest of the pharma industry in covalent inhibitors. We have recently introduced an enzyme mechanism‐based method, EMBM, as a computational tool for binding trend analysis and prediction of chemical sites (<italic>CS</italic>) of reversible covalent enzyme inhibitors. In the current study we demonstrate the utility of EMBM to structure‐based applications. In this mode, the energy of the enzyme‐inhibitor covalent bond is accounted for by the <italic>W</italic>1 and <italic>W</italic>2 covalent descriptors we have developed, whereas the non‐covalent interactions between the inhibitor <italic>CS</italic> and the enzyme active site can be estimated directly on the 3D structure of the enzyme‐inhibitor complex.</p> </abstract>