IN-SILICO ANALYSIS OF DELETERIOUS SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) OF LEUKEMIA INHIBITORY FACTOR (LIF), AND THEIR CONFORMATIONAL PREDICTIONS

Main Article Content

Maham Afzal
Umer Ali
Adeel Riaz
Fouzia Tanvir
Asif Bilal
Sibtain Ahmad

Keywords

LIF, nsSNPs, Molecular docking, Molecular dynamic simulation

Abstract

Leukemia inhibitory factor (LIF) is a multifunctional gene belonging to the interleukin-6 cytokine family. It plays crucial roles in various biological processes such as neuron development, wound healing, maintenance of adrenocorticotropic hormonal secretions in the pituitary glands, reproductive system, and alveolus development. Previous studies have associated LIF polymorphisms with female infertility, schizophrenia (SCZ), and osteoporosis. However, comprehensive computational analyses examining the functional and structural impacts of damaging non-synonymous single-nucleotide polymorphisms (nsSNPs) in LIF have not been conducted. The main objective of this study was to identify and classify nsSNPs that have the most detrimental effects on the LIF gene. A total of nine deleterious mutations (C156F, C153G, L147P, Y111C, Q70H, Y66C, Y66H, T120N, and V164M) were detected, which resulted in altered protein structure. Subsequently, these deleterious mutations were assessed for potential post-translational modification sites using molecular docking and molecular dynamic simulation techniques. The results revealed that the C156F mutant displayed greater conservation and structural dissimilarity compared to the other mutants. Docking analysis demonstrated that EC330 inhibits LIF/LIF-R signaling, thereby impeding LIF's tumor-promoting effects. This finding suggests that EC330 could be a potential candidate for targeted cancer therapy in cases where LIF is overexpressed in malignancies.


 

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