Determinants of Orexin Receptor Binding and ActivationA Molecular Dynamics Study
Abstract
We assess the stability of two previously suggested binding modes for the neuropeptide orexin-A in the OX2 receptor through extensive molecular dynamics simulations. As the activation determinants of the receptor remain unknown, we simulated an unliganded receptor and two small-molecular ligands, the antagonist suvorexant and the agonist Nag26 for comparison. Each system was simulated in pure POPC membrane as well as in the 25% cholesterol–POPC membrane. In total, we carried out 36 μs of simulations. Through this set of simulations, we report a stable binding mode for the C-terminus of orexin-A. In addition, we suggest interactions that would promote orexin receptor activation, as well as others that would stabilize the inactive state- Dataset
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- Biophysics
- Biochemistry
- Medicine
- Cell Biology
- Genetics
- Molecular Biology
- Neuroscience
- Pharmacology
- Sociology
- Cancer
- Computational Biology
- Biological Sciences not elsewhere classified
- Chemical Sciences not elsewhere classified
- unliganded receptor
- orexin receptor activation
- small-molecular ligands
- binding modes
- POPC membrane
- neuropeptide orexin-A
- binding mode
- Orexin Receptor Binding
- OX 2 receptor
- activation determinants
- dynamics simulations
- antagonist suvorexant
- agonist Nag 26
- 36 μ