Species-Specific Binding Affinities of Ad5 Fiber Protein to CAR Receptors: Implications for Adenoviral Vector Design in Drug Delivery and Gene Therapy
International Pharmacy Acta,
Vol. 7 No. 1 (2024),
24 July 2024
,
Page e4: 1-7
https://doi.org/10.22037/ipa.v7i1.46304
Abstract
Adenoviruses play a critical role in molecular biology and gene therapy due to their interaction with coxsackie and adenovirus receptors (CAR). Human adenovirus type 5 (Ad5) has been widely used in the design of gene vectors for therapeutic applications, particularly in drug delivery and gene therapy. This study aims to compare the structural and molecular interactions between Ad5 fiber protein and CAR receptors from humans and mice to enhance the design of adenoviral vectors for drug delivery systems and gene therapy. Amino acid sequences of the Ad5 fiber protein and CAR receptors from humans and mice were obtained from the Protein Data Bank (PDB) and UniProt database. These structures were refined using molecular dynamics simulations and analyzed using the I-TASSER system and GalaxyRefine server. Quality assessments included Ramachandran plot analysis and ProSA-web Z-score calculations. Molecular docking analysis was performed using ClusPro 2.0 to compare the binding affinities. Refinement of hCAR and mCAR models showed significant structural improvements, with residues in favorable areas increasing to 80.3% for hCAR and 78.3% for mCAR. The Z-scores also improved, indicating better structural stability. Molecular docking revealed that mCAR had a stronger binding affinity to the Ad5 fiber protein than hCAR, suggesting species-specific differences in adenoviral infection mechanisms. This study highlights the importance of species-specific CAR receptor interactions in the design of adenoviral vectors. The stronger binding affinity of mCAR for Ad5 fiber protein suggests distinct drug and gene delivery mechanisms in mice compared to humans. These insights are crucial for developing more effective adenoviral vectors for targeted therapeutic applications.
- Adenovirus type 5
- Fiber protein
- Coxsackievirus and adenovirus receptor (CAR)
- In silico analysis
- Molecular docking
- Gene therapy
- Adenoviral vectors
How to Cite
References
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