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 language | English |
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Pages (from-to) | 36-42 |
Number of pages | 7 |
Journal | Molecular Informatics |
Volume | 33 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Bibliographical note
Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimKeywords
- Enzyme inhibitors
- Proteases
- Quantitative structure-activity relationship
- Structure-based drug design
- Transition-state analog