Complexation of peptide epitopes with G4-PAMAM dendrimer through ligand diffusion molecular dynamic simulations
| Autor: | Rolando Alberto Rodríguez-Fonseca, José Correa-Basurto, Martiniano Bello |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Dendrimers
Molecular binding Nanoparticle Peptide Molecular Dynamics Simulation 010402 general chemistry Ligands 01 natural sciences Molecular mechanics Dissociation (chemistry) Molecular dynamics Epitopes Computational chemistry Dendrimer 0103 physical sciences Materials Chemistry Physical and Theoretical Chemistry Spectroscopy chemistry.chemical_classification 010304 chemical physics Chemistry Computer Graphics and Computer-Aided Design 0104 chemical sciences Nylons Nanocarriers Peptides |
| Zdroj: | Journal of molecular graphicsmodelling. 96 |
| ISSN: | 1873-4243 |
| Popis: | Peptide epitopes from HIV-1 gp120 have been used to block the gp120-CD4 complex, whereas their poor absorbable or immunogenic properties prevent them from coupling to generation four polyamidoamine (PAMAM-G4) dendrimers. PAMAM-G4 are synthetic nanoparticles that are relatively nontoxic and nonimmunogenic have been employed as nanocarriers. In a previous study, two peptide epitopes (ABC and PGV04) from gp120 located at the protein-protein interface of the gp120-CD4 complex were identified through protein-protein dissociation. Then, their complexation with G4-PAMAM was evaluated through experimental and theoretical approaches, revealing a stoichiometry of 1:8/9 for G4-PAMAM and ABC or PGV04, respectively, providing important information that can be used to gain insight into the structural and energetic basis of the molecular binding of these G4-PAMAM-peptide systems. In this contribution, we performed ligand diffusion molecular dynamic simulations (LDMDSs) using 1.5 μs combined with the molecular mechanics generalized Born surface area (MMGBSA) approach, a strategy that successfully reproduced experimentally encapsulation on PAMAM-G4-ligand complexes, to explore the mechanism through which ABC and PGV04 are encapsulated by PAMAM-G4 under neutral and acid conditions. Our results reproduce the reported PAMAM-G4-peptide complex stoichiometry, revealing a slower peptide delivery at neutral conditions and a spontaneous release under acidic conditions. LDMDSs show that several peptides can reach stable G4-PAMAM complexes at neutral pH, and only a few are able to encapsulate on dendrimers without impacting dendrimer sphericity. Energetic analysis exploring different generalized Born models revealed that the ABC peptide has better binding properties than PGV04. |
| Databáze: | OpenAIRE |
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