Publication Date: 2024/02/09
Abstract: Dystrophin is one of the most significant and well-researched cytoskeletal proteins that is prominently expressed in skeletal and cardiac muscles. It is a large 400-kD protein, which is encoded by the largest gene in the human body- DMD gene. A significant decrease in dystrophin levels in muscles results in a gradual and severe skeletal muscular weakening. Lack of dystrophin results in muscular dystrophies such as DMD (Duchenne muscular dystrophy) and BMD (Becker muscular dystrophy. Understanding the dystrophin protein's structure is crucial for developing a cure for the disease. Comprehensive knowledge of protein conformation can offer essential insights for protein engineering and medication development. Currently complete structural information about dystrophin protein is not available, only the structure of N-terminal domain and spectrin repeats of central rod domain has been prepared. Our study aims to determine the structure of the C-terminal domain using the structural modelling software (Robetta and Phyre2) and perform the validation of the most accurate structure using the SAVESv6.0 software. The result was concluded on the following basis – 1. PROCHECK (Ramachandran plot) analysis - Robetta predicted model has 90.8% residues in the most favored region and only 0.7% residues in the disallowed region which makes it a good quality model, compared to the phyre2 predicted model where only 69% residues were in the most favored region with 7.0% residues in the disallowed region. 2. ERRAT analysis- Robetta predicted structure is the most accurate with 88.316% as the overall model quality which is more than the phyre2 model quality (64.127%). The study validates Robetta predicted C- terminal domain model as the most stable C-terminal structure of Dystrophin protein.
Keywords: DMD Gene; Dystrophin Protein; Phyre2; Ramachandran Plot; Robetta.
DOI: https://doi.org/10.5281/zenodo.10639763
PDF: https://ijirst.demo4.arinfotech.co/assets/upload/files/IJISRT24JAN1933.pdf
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