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Gain of native conformation of Aurora A S155R mutant by small molecules
Author(s) -
Tanwar Garima,
Purohit Rituraj
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28387
Subject(s) - mutant , aurora kinase , docking (animal) , ectopic expression , aurora a kinase , kinase , microbiology and biotechnology , protein kinase a , aurora inhibitor , chromosome segregation , target protein , biology , chemistry , biochemistry , genetics , cell culture , cell , chromosome , cell cycle , gene , medicine , nursing
Aurora A is a mitotic serine/threonine kinase protein that is a proposed target of the first‐line anticancer drug design. It has been found to be overexpressed in many human cancer cells, including hematological, breast, and colorectal. Here, we focus on a particular somatic mutant S155R of Aurora kinase A protein, whose activity decreases because of loss of interaction with a TPX2 protein that results in ectopic expression of the Aurora kinase A protein, which contributes chromosome instability, centrosome amplification, and oncogenic transformation. The primary target of this study is to select a drug molecule whose binding results in gaining S155R mutant interaction with TPX2. The computational methodology applied in this study involves mapping of hotspots (for uncompetitive binding), virtual screening, protein–ligand docking, postdocking optimization, and protein–protein docking approach. In this study, we screen and validate ZINC968264, which acts as a potential molecule that can improve the loss of function occurred because of mutation (S155R) in Aurora A. Our approaches pave a suitable path to design a potential drug against physiological condition manifested because of S155R mutant in Aurora A.