In Silico Assessment of Post Translational Modifications Caused by NRAS Gene SNPs in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a blood cancer and a malignant disorder of the bone marrow in which hematopoietic precursors are ceased at an early stage of development, preventing them from differentiating. The NRAS gene plays a vital role in regulating cell division. The mutation in this gene leads to an increased activity of the RAS pathway, increased proliferation and decreased apoptosis rates which causes AML. Objective: To identify the deleterious SNPs involved in AML and to further analyze them using bioinformatics tools. Methods: The missense nsSNPs (Q61H, Q61L, G13V, G13R, and G12A) of NRAS were retrieved from NCBI databases. Results: Using in silico analysis, it was found that these pathogenic SNPs could disrupt the protein stability. These mutations were present in the conserved region and had the potential to significantly alter the protein's secondary structure and impair its functionality. The structural effect of mutations was observed by generating 3D models. Post-translational modifications (PTMs) of proteins refers to the chemical modifications that occur after a protein is formed to make it functionally capable. Analyzing PTMs via in silico analysis revealed that missense mutations affect protein functionality. The level of methylation was significantly high in AML patients. These SNPs might affect additional proteins which are functionally associated. Conclusions: The highlighted SNPs could be suitable targets for future research on proteins, biological markers, and medical diagnosis.