The default settings were used in the definition of the interactions, where the following parameters were applied: H-bonds: distance of 2.5 Å between the donor and acceptor with ≥120° and ≥90° for donor and acceptor angles, respectively; π-cation interactions: 4.5 Å distance between the positively charged and aromatic group; π-π interactions: stacking of two aromatic groups face-to-face or face-to-edge; water bridges: distance of 2.8 Å between the donor and acceptor with ≥110° and ≥90° for donor and acceptor angles. Minimum distances between selected atom(s) and water were monitored by trajectory_asl_monitor.py script (Schrödinger LLC). For selected analysis, replica trajectories were merged before the analysis using trj_merge.py script (Schrödinger LLC). The output was transformed to csv-format by st2csv.py (Schrödinger LLC) and plotted by seaborn (v0.11.2). Visualization of the electron density data was conducted with Protein Data Bank in Europe's (PDBe) 3D-visualizer Mol* . WaterMap illustrations were made with PyMOL (The PyMOL Molecular Graphics System, Version 2.5.0 Schrödinger, LLC).