The first 20 snapshots from the NMR ensemble were used to initiate molecular dynamics (MD) simulations (Figure ). Semi-empirical quantum mechanical (SQM) MD was carried out using GFN2-xTB[116] with D3 dispersion[126], as implemented in a developer version of TeraChem v1.9 . The conductor-like polarizable continuum model (C-PCM) was employed with a dielectric of 78.39 for water and a cavity generated from 1.2x Bondi's van der Waals radii[130] for all atoms, as implemented in TeraChem . These simulations were carried out in the NVT ensemble with an initial temperature of 300 K and a timestep of 0.5 fs. The Langevin thermostat was used with a damping frequency of 1 ps -1 .