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Title: Pharmacophore modelling, 3D-QSAR and docking study of HIV inhibitor
Authors: Lisina, K V
Piramanayagam, Shanmughavel
Keywords: HIV;Nucleocapsid protein domain p7;Pyridinioalkanoylthioesters;Pharmacophore;3D-QSAR;Docking
Issue Date: Jan-2018
Publisher: NISCAIR-CSIR, India
Abstract: Human immunodeficiency virus (HIV), the causative virus for acquired immunodeficiency syndrome (AIDS) has become the world’s greatest dispute. Inhibition of nucleocapsid protein domain 7 NCp7 receptors have been sturdily pursued as a promising target for the treatment HIV AIDS. A set of 36 thioesters derivatives has been reported as HIV NCp7 inhibitor was analyzed by employing PHASE method to inspect the structural requirements for diverse analogues to inhibit NCp7 receptors and to obtain a highly predictive model used for designing of novel NCp7 receptors inhibitors. A united study of pharmacophore prediction, atom based 3D-quantitative structure–activity relationship (QSAR) and molecular docking approaches were carried out on pyridinioalkanoyl thiolesters derivatives to understand their structural requisites and binding mode of the best fitted ligand for NCp7 inhibitory activity. Five point pharmacophore hypothesis AADDR (two acceptors, two hydrogen donor, one aromatic ring) yielded a statistically significant 3D-QSAR model with partial least square (PLS) factors 5, regression coefficient value of (R2) = 0.9625, cross validation coefficient value of (Q2) = 0.7775, root mean square error (RMSE) = 0.1358. The core structure of nucleocapsid NCp7 domain is docked with the compounds obtained from ZINC and NCI. Docking study also revealed the binding orientation of active ligands at active residues of NCp7. Using pharmacophore based database search, 3D-QSAR and docking studies, we identified ZINC29569253 as a stable inhibitor. The geometry and type of this pharmacophore model give emphasis to important binding features which will be useful for the design of selective HIV NCp7 inhibitors.
Page(s): 160-175
ISSN: 0975-0967 (Online); 0972-5849 (Print)
Appears in Collections:IJBT Vol.17(1) [January 2018]

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