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- Title
Protein-Protein Interactions: Insight from Molecular Dynamics Simulations and Nanoparticle Tracking Analysis.
- Authors
Chong, Wei Lim; Chupradit, Koollawat; Chin, Sek Peng; Khoo, Mai Mai; Khor, Sook Mei; Tayapiwatana, Chatchai; Nimmanpipug, Piyarat; Thongkum, Weeraya; Lee, Vannajan Sanghiran
- Abstract
Protein-protein interaction plays an essential role in almost all cellular processes and biological functions. Coupling molecular dynamics (MD) simulations and nanoparticle tracking analysis (NTA) assay offered a simple, rapid, and direct approach in monitoring the protein-protein binding process and predicting the binding affinity. Our case study of designed ankyrin repeats proteins (DARPins)—AnkGAG1D4 and the single point mutated AnkGAG1D4-Y56A for HIV-1 capsid protein (CA) were investigated. As reported, AnkGAG1D4 bound with CA for inhibitory activity; however, it lost its inhibitory strength when tyrosine at residue 56 AnkGAG1D4, the most key residue was replaced by alanine (AnkGAG1D4-Y56A). Through NTA, the binding of DARPins and CA was measured by monitoring the increment of the hydrodynamic radius of the AnkGAG1D4-gold conjugated nanoparticles (AnkGAG1D4-GNP) and AnkGAG1D4-Y56A-GNP upon interaction with CA in buffer solution. The size of the AnkGAG1D4-GNP increased when it interacted with CA but not AnkGAG1D4-Y56A-GNP. In addition, a much higher binding free energy (∆GB) of AnkGAG1D4-Y56A (−31 kcal/mol) obtained from MD further suggested affinity for CA completely reduced compared to AnkGAG1D4 (−60 kcal/mol). The possible mechanism of the protein-protein binding was explored in detail by decomposing the binding free energy for crucial residues identification and hydrogen bond analysis.
- Subjects
PROTEIN-protein interactions; MOLECULAR dynamics; HIV; HYDROGEN analysis; BUFFER solutions; HYDROGEN bonding
- Publication
Molecules, 2021, Vol 26, Issue 18, p5696
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules26185696