Molecular Modeling of Sulfonylmorpholinopyrimidines as the Ataxia Telangiectasis Mutated and RAD3-related (ATR) Protein Kinase Inhibitors by Computational Explorations
34 novel ATR inhibitors were used to build an optimal 3D-QSAR model. Homology modeling
and molecular docking were used to study the interaction of ATR kinase protein and inhibitor.
The results showed that both the CoMFA model (q2 = 0.550; r2 = 0.978; standard error of estimate
[SEE] = 0.129; F = 177.729 and r2pred = 0.530) and the CoMSIA model (q2 = 0.632; r2 = 0.991; standard
error of estimate [SEE] = 0.088; F = 277.224 and r2
pred = 0.322) are acceptable. The 3D-model of
ATR kinase was further assessed by ERRAT, WHATCHECK and PROCHECK, which showed that
the final model is reliable with 78.9% of the residues in the most favored regions. According to molecular
docking, Ala562, Ser563, Leu564 and Lys585 were the vital amino acid residues to the ATR kinase. This article
can support useful information for designing novel and high bioactive ATR kinase inhibitors.
Keywords: ATR inhibitor, 3D-QSAR, CoMFA, CoMSIA, Homology modeling, Molecular docking.
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