همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Novel Anti-ageing Strategy Via Targeting CST With Vitamin B1

نویسندگان :

SeyedMobin Mousavi Ghomi¹ Maryam Azimzadeh Irani² Aida Arezoumandchafi³

1- دانشگاه شهید بهشتی 2- دانشگاه شهید بهشتی 3- دانشگاه شهید بهشتی

کلمات کلیدی :

Aging،CST complex،Telomere maintenance،Vitamin B1،Molecular docking

چکیده :

Biological aging is a complex and inevitable process (López-Otín et al., 2013). Cellular and tissue functionality declines progressively, and diseases associated with aging are developed. One of the hallmarks of aging at the molecular dimension is telomere shortening (Blackburn et al., 2006), which contributes to the promotion of cellular senescence and genomic instability. The CST (Ctc1-Stn1-Ten1) complex is essential for the accurate replication and protection of the telomere (Gu et al., 2012), serving as a promising target for anti-aging therapies. Although the catalytic function of telomerase has been thoroughly investigated concerning telomere upkeep (Greider & Blackburn, 1989), recent research indicates the potential for targeting the CST complex (Gu et al., 2012). Furthermore, there is an increasing interest in the influence of micronutrients, including vitamin B1, on the regulation of cellular mechanisms associated with telomere activity and senescence (Selhub et al., 2010). The potential of vitamin B1 as a modulator of the CST complex activity in aging and telomere maintenance was examined in this work. MODELLER (Sali & Blundell, 1993) was used to model the missing residues and complete the crystal structure of the CST complex (PDB ID: 8D0B). Molecular docking simulations were used to examine the optimized structure's binding affinity with vitamin B1, which was obtained from PubChem (2023). Docking was carried out using AutoDock MGL tools (Trott & Olson, 2010), and a grid box was established around the anticipated active site of the CST complex. The binding energy and important molecular interactions of the resultant binding poses were then examined. The binding energy of the best-ranked docking pose of vitamin B1 was -4.8 kcal/mol, showing that this compound interacts favorably with the CST complex. Key interactions involved amino acid residues important for the functionality of the complex; thus, it suggests that vitamin B1 may affect CST-mediated telomere processes. These findings support the potential of vitamin B1 as a modulator of the CST complex and offer a foundation for the development of anti-aging therapeutic strategies. High-throughput screening of large chemical libraries using sophisticated computational methods like molecular docking, virtual screening, and machine learning algorithms will be essential to find strong and specific CST modulators. The development of innovative therapeutic strategies to modulate telomere maintenance and potentially lessen the effects of aging will be made possible by these approaches, which will make it possible to identify compounds with high binding affinity, selectivity for the CST complex, and favorable drug-like properties.