In silico screening of phytochemicals against human caspase-6 for Huntington's disease therapeutics

Abstract

Huntington’s disease (HD) is a fatal genetic disorder caused by a Cytosine-Adenine-Guanine (CAG) repeat expansion in the huntingtin gene. This study utilized a structure-based in silico virtual screening strategy via AutoDock Vina to discover competitive caspase-6 inhibitors from a library of 50 phytochemicals native to the Jahangirnagar University (JU) campus. Protocol accuracy was confirmed by an internal self-docking control yielding a root mean square deviation (RMSD) of < 2.0Å. The 50 plant compounds exhibited binding free energies ranging from −2.1 kcal/mol to −7.1 kcal/mol. There were three major potential therapeutic leads which included Andrographolide (−7.1 kcal/mol), Myricitrin (−7.0 kcal/mol), and Dasycarpidan-1-methanol (−6.7 kcal/mol). The spatial interactions have shown that these molecules can form very stable complexes by virtue of strong hydrogen bonding and hydrophobic pi-alkyl packing near the conserved Cys163-His121 catalytic diad. Since they have low molecular weight, these phytochemicals may present themselves as potential candidates against HD.