Pharmacophore Generation and 3D-QSAR Model Development Using PHASE
Nowadays, the prediction of biological activity of novel compounds is one of the major challenges in drug design. Toward this aim a useful procedure is the development and application of predictive computational models using three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, which can decrease the cost and time of biological experiments. In this chapter, the use of application PHASE is analyzed, which is a recent but already widespread method for pharmacophore- or atom-based 3D-QSAR model building. The main steps of procedure provided by PHASE are described, and a general workflow and important practical notes are referred. An attempt in order to design new chemotypes with enhanced cytotoxicity against K562 cells is also provided as an example for the 3D pharmacophore model generation on 33 novel (E)-α-benzylthiochalcones.
Key words3D-QSAR Chalcones Pharmacophore alignment Pharmacophore model PHASE
The corresponding author Eleni Vrontaki (E.V.) acknowledges funding by State Scholarships Foundation (IKY postdoctoral fellowship, MIS 5001552, NSRF 2014–2020).
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