Molecular Modelling and Evaluation of Hidden Information in ABCB۱۱ Gene Mutations

Background: Cholestatic disorders are divided in the extra and intra-hepatic that created due to the severe liver diseases. ABCB۱۱ encodes the bile salt export pump and this gene is mutated in several forms of intrahepatic cholestasis. So far, some molecular features of this gene was studies. Objective: Using a developed web server, we identified high number of rare codons in this gene, and four cases were related to BSEP-deficient patients which can be used for drug design. Material and Methods: By in-silico modelling of ABCB۱۱, some of rare codons in different locations of ATP۸b۱ gene were identified and evaluated. Using several web servers a number of mutations that converted non-rare codons to rare codon in these patients were identified. Results: Some of these rare Codons were located at special positions by mutation of which, the new side chains do not seem suitable for protein structure and function. Furthermore, this mutation changed the protein folding rate that may have a critical role in proper folding. Thus, primary change of these codons contributes to BSEP deficiency. Conclusion: This work is a comprehensive analysis of rare codons of ABCB۱۱ and assessment of a number of these rare codon in protein levels. Rare codons evaluation can enhance our understanding of ABCB۱۱ structural protein of ABCB۱۱, and help us to develop mutation-specific therapies in design of new drugs.

Keywords:

ABCB۱۱ , Bioinformatics analysis , Rare codon , Mutation