In Silico Prediction of Potential pTLR7/pSTING Dual-Targeting Ligands via Virtual Screening and Molecular Dynamics...

Area of Science:

• Immunology and Veterinary Pharmacology
• Computational Drug Discovery

Background:

• Toll-like receptor 7 (TLR7) and Stimulator of Interferon Genes (STING) ligands exhibit significant immunomodulatory effects, including anti-infection, anti-tumor, and autoimmune disease alleviation.
• Developing effective immunomodulators for livestock is crucial for animal health and disease prevention.

Purpose of the Study:

• To screen for dual-target livestock immunomodulators targeting porcine TLR7 (pTLR7) and porcine STING (pSTING).
• To identify novel compounds with high binding affinity and favorable pharmacokinetic properties for pTLR7 and pSTING.

Main Methods:

• Employed molecular docking and virtual screening techniques to identify potential dual-target immunomodulators.
• Utilized molecular dynamics (MD) simulations to assess the stability of ligand-protein complexes.
• Analyzed protein similarity across species (pigs, humans, mice) and predicted structure-activity relationships (SAR).

Main Results:

• Two compounds (Compound 2 and Compound 7) demonstrated high molecular docking scores, exceeding those of positive controls.
• MD simulations confirmed stable complex formation between the identified compounds and both pTLR7 and pSTING.
• Calculated binding free energies for Compound 2 and Compound 7 were comparable to positive controls, indicating strong binding affinity.

Conclusions:

• Compound 2 and Compound 7 are predicted to form stable complexes with pTLR7 and pSTING, possessing satisfactory physicochemical and pharmacokinetic characteristics.
• These compounds represent promising candidates for experimental validation as novel livestock immune enhancers.
• The study provides a foundational basis for the development and structural modification of animal immune enhancers.