• UMA KUMARI (first Author)
• Ekta Tyagi (First Author)
• Nehal Balhara (Second Author)
• Ojas Singh (Second Author)

Huntington’s disease (HD) is a destructive genetic condition inherited dominantly, primarily caused by the expansion of CAG repeats in exon 1 of the Huntington gene on chromosome 4. This expansion results in the production of mutant forms of the huntingtin protein (m HTT) with abnormal polyglutamine sequences, initiating the disease’s progression. The initial 17 residues of amino acids in huntingtin protein [HTT(1 17)] are critical in defending against various pathological manifestations both in laboratory experiments and in living organisms. A recent study investigates how a single chain variable fragment (scFv) known as C4 effectively blocks the formation of amyloid structures by exon1 fragments of huntingtin under laboratory conditions. The research also explores the structural mechanisms underlying this inhibition and protection by analyzing the crystal structure of the C4 scFv and HTT(1 17) complex. The peptide interacts with specific residues (3 11), forming an amphipathic helix that binds to the antibody fragment. This binding occurs within a dimeric C4 scFv: HTT (1 17) complex, involving the hydrophobic surface and β sheet interface. Further, elucidation through high resolution NMR and physicochemical analysis in solution provides deeper insights into how C4 scFv effectively prevents HTT aggregation, thus demonstrating its potential as a therapeutic candidate. Furthermore, computational analysis will be conducted to assess the structural properties, total protein atoms, domains, and functions of protein samples of Huntington homologs related to a protein sequence of interest. This will be followed by an interactive examination of sequence structure relationships, active sites, and bound chemicals. Active site identification is done using the PDB file format in PyMOL. Drug designing will be performed to study the interaction of Huntington’s Disease receptors with associated ligands. Quality estimation of protein structure using server PROCHECK, ERRAT, and Ramachandran plot which identifies possible secondary structure protein can adapt. The alignment program uses clustal omega and InterPro Scan to generate a phylogenetic tree. CADD is used to dock the appropriate ligand to the binding site of the protein. Finally, STRING was used to determine potential protein-protein interaction.

Key Words,Huntington’s disease, Drug designing, Quality estimation of protein, protein protein interaction, structural analysis, phylogenetic relationships.

"COMPUTATIONAL ANALYSIS AND STRUCTURE-BASED DRUG DESIGN FOR MISFOLDING OF HUNTINGTON’S DISEASE FRAGMENT", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.11, Issue 4, page no.h251-h265, April-2024, Available :http://www.jetir.org/papers/JETIR2404731.pdf

"COMPUTATIONAL ANALYSIS AND STRUCTURE-BASED DRUG DESIGN FOR MISFOLDING OF HUNTINGTON’S DISEASE FRAGMENT", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.11, Issue 4, page no. pph251-h265, April-2024, Available at : http://www.jetir.org/papers/JETIR2404731.pdf