Interaction of rat α9α10 nicotinic acetylcholine receptor with α-conotoxin RgIA and Vc1.1: Insights from docking, molecular dynamics and binding free energy contributions
| Autor: | Jiemei Jiang, Yuanyuan Tian, Xincan Li, Danrui Liu, Yong Wu, Sulan Luo, Ying Fu, Rui Li, Donting Zhangsun |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Binding free energy Protein subunit Quantitative Structure-Activity Relationship Molecular Dynamics Simulation Receptors Nicotinic 03 medical and health sciences Molecular dynamics 0302 clinical medicine Materials Chemistry Animals Amino Acid Sequence Amino Acids Physical and Theoretical Chemistry Spectroscopy α conotoxin Binding Sites Chemistry Computer Graphics and Computer-Aided Design Experimental research Rats Molecular Docking Simulation Nicotinic acetylcholine receptor 030104 developmental biology Docking (molecular) Biophysics Conotoxins 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Journal of Molecular Graphics and Modelling. 92:55-64 |
| ISSN: | 1093-3263 |
| DOI: | 10.1016/j.jmgm.2019.06.020 |
| Popis: | The α9α10 nicotinic acetylcholine receptor (nAChR) is an effective therapeutic target for neuropathic pain. α-Conotoxin RgIA and Vc1.1 are two well-known peptides blocking α9α10 nAChR potently and selectively, which have been extensively investigated as drug candidates. Several key residues were established in previous experimental research. However, the mechanism of the specific interaction still needs to be elucidated in more detail. In this work, we explored the interaction mechanism between RgIA/Vc1.1 and rat α9α10 nAChR using docking and molecular dynamics (MD) simulations. Energy and network analysis programs were used to reveal key residues responsible for their interaction. Our results indicated that the most critical residues were in accord with previous studies. Importantly, several novel residues, including Tyr95, Trp151 in α9 (+)α10 (-) interface as well as Tyr196, Arg59in α10 (+)α9 (-) interface, were found in our models. Furthermore, we analyzed noncovalent interaction energies between RgIA/Vc1.1 and rat α9α10 nAChR. The results showed that three negatively charged residues (Glu197 in α10 subunit, Asp168 in α9 subunit and Asp205 in α10 subunit) were involved in the interaction between RgIA and rat α9α10 nAChR. In contrast, the interaction between Vc1.1 and rat α9α10 nAChR was mediated by the positively charged residues Arg59, Arg81 in α9 (-) subunit. These findings provided further insights into the molecular mechanisms of interaction between RgIA and Vc1.1 and rat α9α10 nAChR. |
| Databáze: | OpenAIRE |
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