Effects of Normal and Aberrant Glycosylation on the Stability of α1-Anti Trypsin Through Molecular Dynamic Simulation

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.