Dietary compounds activates sirtuins - a computational modeling approach towards the management of ageing

Area of Science:

• Biogerontology
• Computational Drug Design
• Molecular Biology

Background:

• Sirtuin proteins are key regulators of lifespan and age-related diseases.
• Dietary bioactive compounds are being explored for their potential to modulate sirtuin activity.
• Aging is a complex biological process involving cellular pathways influenced by sirtuins.

Purpose of the Study:

• To identify natural bioactive compounds that can modulate sirtuin proteins (SIRT 1, 3, 6, 7) using computational methods.
• To explore the potential of these compounds in the context of aging and age-related diseases.
• To present a novel computational approach for discovering anti-aging compounds.

Main Methods:

• High throughput virtual screening (HTVS) using AutoDock-VINA to identify candidate compounds.
• Molecular dynamics (MD) simulations using GROMACS to analyze compound-protein interactions.
• In silico drug design techniques applied to natural compounds from dietary sources.

Main Results:

• Several natural compounds, including fagopyrine, emblicanin B, epicatechin, withanolide, and dulcisisoflavone, showed high binding affinity to sirtuin proteins (docking scores from -12.7 to -7.2 kcal/mol).
• MD simulations confirmed stable interactions between the identified compounds and target sirtuins over 100 ns.
• No significant conformational changes were observed in the protein structures during simulations.

Conclusions:

• Computational drug design effectively identified promising natural compounds for sirtuin modulation.
• These findings support the potential of dietary bioactive compounds as therapeutic agents for healthy aging.
• The study provides a foundation for future experimental validation of these compounds in anti-aging strategies.