Application of EMBM to structure-based design of warheads for protease inhibitors

Tamar Traube, Michael Shokhen, Amnon Albeck

Research output: Contribution to journalArticlepeer-review

Abstract

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 (CS) 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 W1 and W2 covalent descriptors we have developed, whereas the non-covalent interactions between the inhibitor CS and the enzyme active site can be estimated directly on the 3D structure of the enzyme-inhibitor complex.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalMolecular Informatics
Volume33
Issue number1
DOIs
StatePublished - Jan 2014

Bibliographical note

Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • Enzyme inhibitors
  • Proteases
  • Quantitative structure-activity relationship
  • Structure-based drug design
  • Transition-state analog

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