Effects of Normal and Aberrant Glycosylation on the Stability of α1-Anti Trypsin Through Molecular Dynamic Simulation
Mujeeb Alam Khan, Ehtesham, Muhammad Shoaib, Roshan Ali, Muhammad Idrees.
3066
ABSTRACT
The Alpha-1 antitrypsin belonging to serpin family
is a protease inhibitor, the level of which rises by a factor of ten during
inflammation
Purpose: To
investigate the stability of normal and aberrantly glycosylated α1-antitrypsin
through molecular dynamics simulation
Study Design: Experimental study
Methodology: Current project was
conducted in the department of Biochemistry at Institute of Basic Medical
Sciences Khyber Medical University, Peshawar. A1AT FASTA sequence was
retrieved from UniProt database (UniProt ID: P01009). Post-Translational
Modifications (PTM) regions were identified from the same database. GLYCONNECT
database was used to understand N-linked glycation with the asparagine residues
found at position 70, 107, and 271 amino acid residue regions
Statistical
analysis: Different bioinformatics analyses such that
Root Mean Square Deviation, Radius of gyration, Root Mean Square fluctuation,
Hydrogen-bonding, Secondary Structure
Determination, and Principal Component
Analysis were executed for 100 ns molecular dynamics simulation run
Results: RMSd, RMSf, and
Rgyr significantly differ between the native type and cancer isoform. More
H-bonding and strong protein stability and folding were seen in the native
type. PCA analysis further confirms native type compact motion in the parallel
direction during MD simulation
Conclusion: It was concluded that glycated protein appears to have high
structural stability than its aberrant glycated protein. However, it will
be utilized for the prompt production of the anti-cancer drugs to effectively
treating cancer disease
Key Words: Alpha-1 Antitrypsin, Aberrant Glycosylation
and Molecular Dynamic Simulation.