Authors :
Akanksha Mishra; Pramod Sairkar; Nipun Silawat; Mohd. Maruf Khan; Anil Kothari
Volume/Issue :
Volume 9 - 2024, Issue 1 - January
Google Scholar :
http://tinyurl.com/b6fm5am9
Scribd :
http://tinyurl.com/msesnchk
DOI :
https://doi.org/10.5281/zenodo.10639763
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.
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.
