Artificial Intelligence Approach To Investigate the Longevity Drug

Area of Science:

• Gerontology and Pharmacology
• Computational Biology and Bioinformatics
• Traditional Chinese Medicine (TCM) Research

Background:

• Longevity is a significant area of research, with the Klotho protein identified as a key factor.
• Understanding the molecular mechanisms underlying aging and longevity is crucial for developing interventions.
• Traditional Chinese Medicine (TCM) offers a rich source of potential therapeutic compounds.

Purpose of the Study:

• To identify novel Traditional Chinese Medicines (TCMs) targeting key proteins related to longevity, specifically insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (IR).
• To leverage a multi-disciplinary approach combining network pharmacology, machine learning, deep learning, and molecular dynamics (MD) simulations for drug discovery.
• To validate the efficacy and stability of identified TCM candidates through computational methods.

Main Methods:

• Network pharmacology was employed to analyze potential drug-target interactions.
• Multiple machine learning algorithms (nine in total) and a novel deep learning algorithm were utilized to build predictive models for drug efficacy.
• Molecular dynamics (MD) simulations, including a 500 ns run, were performed to assess protein-ligand binding stability and properties.
• Docking studies were conducted between TCM database compounds and target proteins (IGF1R and IR).

Main Results:

• Predictive models demonstrated high accuracy, with R-squared values exceeding 0.87 for training sets and 0.88 for test sets.
• Molecular dynamics simulations confirmed the stability and favorable properties of protein-ligand interactions.
• Three TCMs—Antifebrile Dichroa, Holarrhena antidysenterica, and Gelsemium sempervirens—were identified as potent candidates targeting IGF1R and IR.

Conclusions:

• The study successfully identified novel TCMs with potential therapeutic applications for longevity by targeting key proteins.
• The integrated computational approach provides a robust framework for discovering anti-aging compounds from TCM.
• Antifebrile Dichroa, Holarrhena antidysenterica, and Gelsemium sempervirens warrant further investigation as potential longevity-promoting agents.