In Silico Analysis Predicting the Structural and Functional Effects of High-risk nsSNPs in the Human GCK Gene Associated with Gestational Diabetes

Document Type : Regular Article

Authors

1 Laboratory Biochemistry Environment and Agri-food, Department of Biology, Faculty of Science and Technics Mohammedia, Hassan II University Casablanca, Morocco. Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco

2 Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco

3 Laboratory Biochemistry Environment and Agri-food, Department of Biology, Faculty of Science and Technics Mohammedia, Hassan II University Casablanca, Morocco

10.22036/pcr.2022.349495.2129

Abstract

To assess the effect of missense variants and the degree of pathogenicity of each nsSNP on the function, structure, and stability of the glucokinase protein (GCK), several algorithms were utilized including PHD-SNP, PROVEAN, SNPs&GO, PolyPhen 2.0, SIFT, MutPred, I-Mutant, MUpro, Consurf, and STRING. We have evaluated the flexibility levels of the residues in GCK protein using PredFlexy server and then we used the DynOmics server to study the molecular dynamics and understand the correlated communications between the residues.
Towards the end, TM-align and the PyMol program were used to analyze the topology and structural similarity between the native model and the generated mutants.
In total, seven out of eight nsSNPs were fund to be the most damaging variants and to exhibit a deleterious effect on the structure of the GCK protein, and probably on its function. This in silico study gives information on functional polymorphisms that impact the structure, stability, and function of the GCK protein, and consequently susceptibility to Gestational Diabetes.

Graphical Abstract

In Silico Analysis Predicting the Structural and Functional Effects of High-risk nsSNPs in the Human GCK Gene Associated with Gestational Diabetes

Keywords