• Uma Kumari
• Umang Uniyal (First Author)

Abstract: Parkinson’s disease (PD) is a complex neurodegenerative disorder, with Leucine-Rich Repeat Kinase 2 (LRRK2) playing a pivotal role in its pathology. This study integrates Next-Generation Sequencing (NGS) and structural bioinformatics to investigate the A25T Transthyretin crystal structure of LRRK2, aiming to elucidate its functional and evolutionary significance. A comprehensive computational approach incorporating RasWin, PyMOL (B-factor analysis), InterProScan, Ramachandran plot assessment, STRING, Prosite, BLAST, and ERRAT was employed to assess protein stability, structural integrity, conserved motifs, gene ontology, and functional interactions. BLAST analysis identified conserved regions, while InterProScan and Prosite provided insights into domain architecture, homologous superfamilies, and functionally relevant binding sites. B-factor analysis highlighted structurally dynamic regions, whereas Ramachandran plot validation confirmed stereochemical accuracy. STRING analysis, including the A25T transthyretin variant, identified key protein-protein interactions and gene ontology associations, suggesting a potential link between LRRK2 and neurodegenerative pathways. ERRAT quality assessment further reinforced the structural reliability of 6TXV. Furthermore, Multiple Sequence Alignment (MSA) revealed conserved regions across homologous sequences, shedding light on evolutionary relationships and functionally critical domains relevant to LRRK2’s role in PD. These findings enhance our understanding of LRRK2’s molecular function in PD pathogenesis and provide a foundation for targeted drug discovery and therapeutic interventions.

Parkinson’s Disease, LRRK2, NGS, Structural Analysis, A25T Transthyretin, Sequence analysis, Prosite, MSA

"Next Genration Sequencing Data Analysis of A25T Transthyretin Structure Associated with Parkinson’s Disease", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.12, Issue 3, page no.b612-b622, March-2025, Available :http://www.jetir.org/papers/JETIR2503168.pdf

"Next Genration Sequencing Data Analysis of A25T Transthyretin Structure Associated with Parkinson’s Disease", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.12, Issue 3, page no. ppb612-b622, March-2025, Available at : http://www.jetir.org/papers/JETIR2503168.pdf