The theoretical structure of zwitterion tautomer of muscimol in water modelled explicitly and implicitly was determined.
•
An important role of water molecules in the first solvation shell was demonstrated.
•
The IR and Raman spectra of solid muscimol were observed for the first time.
•
Combined theoretical and experimental data support the presence of zwitterionic form of muscimol in solid state and water.
Abstract
The presented study focuses on the interaction of the well-known neurotoxin muscimol with water. Two approaches for the water solvent are applied – the explicit and the implicit. The muscimol-water clusters were obtained by the molecular dynamics simulations and the first solvation shell was kept for further studies. Implicit water was mimicked via the polarized continuum model (PCM). All three tautomeric forms of the free muscimol molecule are considered in the calculations. The combined theoretical and experimental vibrational IR and Raman studies determined the stability of the prevailing zwitterion form in water. We proved that water molecules in the first solvation shell are crucial for the correct prediction of structural and spectroscopic parameters of muscimol due to its ability to form strong hydrogen bonds. We believe that our findings will shed some light on the binding preferences of muscimol with the γ-aminobutyric acid (GABA) receptor.