Comprehensive characterization of coding and non-coding single nucleotide polymorphisms of the Myoneurin (MYNN) gene using molecular dynamics simulation and docking approaches

• Published in: PloS one 2024-01, Vol.19 (1), p.e0296361-e0296361
• Main Authors: Mou, Sadia Islam, Sultana, Tamanna, Chatterjee, Dipankor, Faruk, Md Omar, Hosen, Md Ismail
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Annotations; Bioinformatics; Biology and Life Sciences; Bladder cancer; Cancer; Care and treatment; Chromosome 3; Chronic diseases; Clinical significance; Colorectal cancer; Development and progression; Gene expression; Gene mutations; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health aspects; Machine learning; Maximum likelihood method; miRNA; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Molecular modelling; Mutation; Nucleotides; Ontology; Pathogenesis; Physical Sciences; Polymorphism; Polymorphism, Single Nucleotide; Predictions; Proteins; R&D; Regulatory sequences; Research & development; Research and Analysis Methods; Simulation; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Structure-function relationships
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0296361

Genome-wide association studies (GWAS) identified a coding single nucleotide polymorphism, MYNN rs10936599, at chromosome 3q. MYNN gene encodes myoneurin protein, which has been associated with several cancer pathogenesis and disease development processes. However, there needed to be a more detailed characterization of this polymorphism's (and other coding and non-coding polymorphisms) structural, functional, and molecular impact. The current study addressed this gap and analyzed different properties of rs10936599 and non-coding SNPs of MYNN via a thorough computational method. The variant, rs10936599, was predicted functionally deleterious by nine functionality prediction approaches, like SIFT, PolyPhen-2, and REVEL, etc. Following that, structural modifications were estimated through the HOPE server and Mutation3D. Moreover, the mutation was found in a conserved and active residue, according to ConSurf and CPORT. Further, the secondary structures were predicted, followed by tertiary structures, and there was a significant deviation between the native and variant models. Similarly, molecular simulation also showed considerable differences in the dynamic pattern of the wildtype and mutant structures. Molecular docking revealed that the variant binds with better docking scores with ligand NOTCH2. In addition to that, non-coding SNPs located at the MYNN locus were retrieved from the ENSEMBL database. These were found to disrupt the transcription factor binding regulatory regions; nonetheless, only two affect miRNA target sites. Again, eight non-coding variants were detected in the testes with normalized expression, whereas HaploReg v4.1 unveiled annotations for non-coding variants. In summary, in silico comprehensive characterization of coding and non-coding single nucleotide polymorphisms of MYNN gene will assist researchers to work on MYNN gene and establish their association with certain types of cancers.