TY - JOUR ID - 159206 TI - In Silico Analysis Predicting the Structural and Functional Effects of High-risk nsSNPs in the Human GCK Gene Associated with Gestational Diabetes JO - Physical Chemistry Research JA - PCR LA - en SN - 2322-5521 AU - Khamlich, Jihane AU - Douiyeh, Imane AU - Saih, Asmae AU - Baggar, Asmae AU - Kettani, Anass AU - Safi, Amal AD - 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 AD - Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik Hassan II University of Casablanca, Morocco AD - Laboratory Biochemistry Environment and Agri-food, Department of Biology, Faculty of Science and Technics Mohammedia, Hassan II University Casablanca, Morocco Y1 - 2023 PY - 2023 VL - 11 IS - 3 SP - 653 EP - 673 KW - GCK KW - Gestational diabetes KW - Missense variants KW - prediction KW - Bioinformatics tools KW - Genetic susceptibility DO - 10.22036/pcr.2022.349495.2129 N2 - 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. UR - https://www.physchemres.org/article_159206.html L1 - https://www.physchemres.org/article_159206_85d2ab620114778a2358868ca0dc67fe.pdf ER -