Structure modeling and mutational analysis of gap junction beta 2 (GJB2)

Abstract

The genome sequencing accomplishes complete genetic blue prints for hundreds of organisms, including humans. In the current era, we are trying to focus on analyzing, controlling and modifying functions of proteins encoded by these genomes. This task is attained by protein three dimensional structures. Three dimensional (3 D) structure is very useful for understanding biological functions. Gap junction beta 2 (GJB2), human gene encoding for gap junction beta 2 protein is involved in various hearing disorders in Pakistani families. After the first report of GJB2 involvement in Pakistani families, it was necessary to further study this protein. Therefore, a 3D structure of GJB2 was developed using comparative modeling approach. For modeling, a template was selected by blastp at NCBI and the best template selected was 2ZW3. By comparing the template-target sequence, a model was created using MODELLER, a program for homology modeling. The accuracy of the predicted structure was checked using Ramachandran plot which showed that the residue falling in the favored region was 92.4%. The predicted GJB2 model can be used to understand the defects that lead to deafness and eventually in drug designing. Domains and different properties of GJB2 were analyzed by applying online servers. Most frequent mutations of GJB2 were discussed by differentiating between damaging and benignity.