Neurogenic locus notch homolog protein 1 (Notch1) SNP informatics coupled with Intrinsically Disordered Region and Post Translational Modifications reveals the complex structural crosstalk of Lung Adenocarcinoma (LUAD)

Abstract

Lung adenocarcinoma (LUAD) is the foremost histological subtype among the lung cancer which is a fundamental root cause in the cancer mortality rate. Prominent documented modifications in lung cancer are notable rates of mutational and cross talking of the signalling pathways. Here we are seeking insight into addressing the structural and functional role of NOTCH1 and associated SNPs in LUAD progression. Our previous study established that NOTCH1 as prognostic marker having a notable high expression in the LUAD and cross talking of Epithelial Mesenchymal Transition (EMT) signalling even though it is down regulated. With the aid of insilico tools the deleterious SNPs were predicted and designated. The highlighted deleterious mutations were characterized through Molecular Docking and dynamics simulations (MDS) studies. The sequential SNP analysis in NOTCH1 resulted in 43 deleterious SNPs and 13 SNPs resulted deleterious and damaging effect. The structural based analysis results three stabilizing SNPs such as S1464I, A1705V and T1602I in the conserved and functional domain of NOTCH1. In addition, 1660–2555 sequence locations were identified as the Intrinsically Disordered Region (IDR) with a score of above 0.5 in the NOTCH1. Moreover the Post Translational Modification (PTM) analysis revealed two key PTM modifications such as o-linked glycosylation and Phosphothreonine within the IDR region which are functional as well as the conserved domains and the most essential role for the LUAD progression. The outcome of our research reflects a potential backdrop of deleterious SNPs of NOTCH1 in LUAD progression through the crosstalk of the Epithelial Mesenchymal Transition signalling.