In the current study, the interaction mechanisms between protonated neurotransmitters: octopamine (4-(2-amino-1-hydroxyethyl)phenol) and norepinephrine (4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol) with the β-1 adrenergic receptor (β1AR) were examined by molecular docking, molecular dynamics (MD) simulations and MM/PBSA free energy calculations. The investigated receptor belongs to the G-protein coupled receptor group. The investigation was carried out at physiological pH=7.4. It was estimated that both compounds exist in the protonated form in the water at physiological pH. It was found that both protonated neurotransmitters established similar interactions with amino acid residues of the receptor, such as salt bridges, conventional hydrogen bonds, π-σ, and T-shaped π-π interactions, as shown by molecular docking simulations. As the initial structures for MD simulation with a total time of 10ns the most stable docking structures were used. The presented results are expected to provide some useful information for the design of specific β1AR agonists.
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