Research Article Open Access

In silico Assessment of the Arg85Trp Glucokinase Mutation Effects

Faiza Bouldjennet1, Souhila Bouaziz-Terrachet1, Malha Azzouz2 and Rachida Raache3
  • 1 University M’Hamed Bougara of Boumerdes, Algeria
  • 2 Mustapha Pacha Hospital, Algeria
  • 3 University of Sciences and Technology Houari Boumediene, Algeria

Abstract

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of autosomal dominantly inherited, young-onset β-cell disorders that account for approximately 2% of non-insulin-dependent diabetics in Europe. MODY2 or GCK-MODY is caused by inactivating heterozygous mutations in the glucokinase. Linkage of MODY to the Arg85Trp GCK mutation, among Algerian diabetic patients has been established in our previous research. The main objective of this study is to strengthen the evidence for the pathogenicity of this mutation using bioinformatics tools. For this purpose, prediction of Arg85Trp mutation effect on glucokinase (PDB ID: 1V4T) stability was performed using I-Mutant 3.0, PoPMuSiC 3.1, DUET and mCSM web servers. Otherwise, structural analysis was performed after optimization of the native and the mutated structures (PDB ID: 1V4T). For that the steepest descent geometries optimization were applied using Nano Molecular Dynamics software (NAMD 2.12). Subsequently, interactions established between the native Arg85 or the mutated Trp85 and the surrounding residues were studied using Accelrys Discovery Studio Visualizer software. In silico analysis conducted through I-Mutant 3.0, PoPMuSiC 3.1, DUET and mCSM softwares, predicts the Arg85Trp as a destabilizing mutation. Structural modeling gives further evidence in favor of the pathogenicity of this mutation. Overall, our results corroborate with the previous metabolic and in silico studies which associate Arg85Trp mutation to MODY phenotype.

Current Research in Bioinformatics
Volume 8 No. 1, 2019, 38-41

DOI: https://doi.org/10.3844/ajbsp.2019.38.41

Submitted On: 25 December 2019 Published On: 27 February 2020

How to Cite: Bouldjennet, F., Bouaziz-Terrachet, S., Azzouz, M. & Raache, R. (2019). In silico Assessment of the Arg85Trp Glucokinase Mutation Effects. Current Research in Bioinformatics, 8(1), 38-41. https://doi.org/10.3844/ajbsp.2019.38.41

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Keywords

  • In silico
  • Glucokinase
  • Arg85Trp Mutation
  • Stability
  • Structural Modeling