An in-silico analysis of OGT gene association with diabetes mellitus.

O-GlcNAcylation is a nutrient-sensing post-translational modification process. This cycling process involves two primary proteins: the O-linked N-acetylglucosamine transferase (OGT) catalysing the addition, and the glycoside hydrolase OGA (O-GlcNAcase) catalysing the removal of the O-GlCNAc moiety on nucleocytoplasmic proteins. This process is necessary for various critical cellular functions. The O-linked N-acetylglucosamine transferase (OGT) gene produces the OGT protein. Several studies have shown the overexpression of this protein to have biological implications in metabolic diseases like cancer and diabetes mellitus (DM). This study retrieved 159 SNPs with clinical significance from the SNPs database. We probed the functional effects, stability profile, and evolutionary conservation of these to determine their fit for this research. We then identified 7 SNPs (G103R, N196K, Y228H, R250C, G341V, L367F, and C845S) with predicted deleterious effects across the four tools used (PhD-SNPs, SNPs&Go, PROVEAN, and PolyPhen2). Proceeding with this, we used ROBETTA, a homology modelling tool, to model the proteins with these point mutations and carried out a structural bioinformatics method- molecular docking- using the Glide model of the Schrodinger Maestro suite. We used a previously reported inhibitor of OGT, OSMI-1, as the ligand for these mutated protein models. As a result, very good binding affinities and interactions were observed between this ligand and the active site residues within 4Å of OGT. We conclude that these mutation points may be used for further downstream analysis as drug targets for treating diabetes mellitus.

Molecular Modeling Studies of Natural Inhibitors of Androgen Signaling in Prostate Cancer.

Prostate cancer is the second most common disease in men and the sixth leading cause of death from cancer globally, with 20 million men expected to be affected by 2024 thus considered as chronic illness which requires immediate attention. As an androgen-dependent illness that relies on the androgen receptor for development and progression, inhibition of the androgen receptor can lead to a therapeutic solution, hence serving as a vital therapeutic target. This study focused on the computational analysis of the inhibitory potentials of Vitis vinifera, a reported plant with anti-cancer properties, against androgen receptor employing molecular docking, ADMET studies, Binding energy study, pharmacophore modeling, and molecular dynamics simulation approaches. After the investigation, it was determined that 5 compounds: cis-piceid, cis-astrigin, gallocatechin, phlorizin, and trans-polydatin, might be possible androgen receptor inhibitors since they had higher docking scores and ADMET qualities than compared standards, with cis-piceid being the best-predicted inhibitor.