Protein-protein interactions: Insight from molecular dynamics simulations and nanoparticle tracking analysis

Chong, Wei Lim and Chupradit, Koollawat and Chin, Sek Peng and Khoo, Mai Mai and Khor, Sook Mei and Tayapiwatana, Chatchai and Nimmanpipug, Piyarat and Thongkum, Weeraya and Lee, Vannajan Sanghiran (2021) Protein-protein interactions: Insight from molecular dynamics simulations and nanoparticle tracking analysis. Molecules, 26 (18). ISSN 1420-3049, DOI

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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 ( increment 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.

Item Type: Article
Funders: Ministry of Higher Education (MOHE) through the Fundamental Research Grant Scheme (FP125-2019A), National Research Council of Thailand (NRCT) (NRCT 808/2563), Office of National Higher Education Science Research and Innovation Policy Council, Program Management Unit for Human Re- sources & Institutional Development, Research and Innovation (B05F630102), National Science and Technology Development Agency (NSTDA), National Research University Project under Thailand's Office of the Higher Education Commission, Center of Excellence for Innovation in Analytical Science and Technology (I-ANALY S-T), Chiang Mai University, Thailand (R000026614)
Uncontrolled Keywords: Nanoparticle tracking analysis; Molecular dynamics simulations; HIV-1; DARPins; Protein-protein binding
Subjects: Q Science > QD Chemistry
R Medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science > Department of Chemistry
Faculty of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 02 Sep 2022 03:20
Last Modified: 02 Sep 2022 03:20

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