Authors: Mohammad Uzzal Hossain, Mohammad Nazmus Sakib, A.B.Z. Naimur Rahman, SM Sajid Hasan, Nazia Hassan Nisha, Arittra Bhattacharjee, Zeshan Mahmud Chowdhury, Ishtiaque Ahammad, Keshob Chandra Das, Mohammad Shahedur Rahman, Md. Salimullah

Abstract

Lung cancer is the predominant form of cancer globally, arising from the dysfunction of genetic mutations. Although PTEN mutation is crucial in the aetiology of lung cancer, the mapping of these major drivers has to be determined. We leverage computational algorithms on 43,855 SNPs of PTEN to discover the mutational impact contributing to lung cancer. Fifteen variations were identified as detrimental, and no pertinent studies have previously addressed their structural and functional aspects. Notably, seven variations were identified as the most significant contributors to lethal effects in functional aberration, as demonstrated by the computational assessment. Subsequently, molecular simulation elucidated the structural instability associated with these alterations. Furthermore, drug binding experiments at the mutational site corroborated the destabilization experiments by demonstrating the conformational alteration of the structure, resulting in varied amino acid interactions. In summary, the present study elucidates the influence of mutations in PTEN structure on its functional architecture.

To access the full article: https://www.biorxiv.org/content/10.1101/2024.10.06.616856v1