During equilibration, we conducted 1000 steps of energy minimisation, and then in the NVT ensemble, applied harmonic constraints to protein and ligand atoms, whilst heating the system from 60K to 310K (an increase of 1K every 2ps). We then ran in the NVT ensemble at 310K for 300ps with no constraints. Following this, we performed equilibration in the NPT ensemble, using a Monte-Carlo barostat with a pressure of 1.01325 bar and frequency of 50fs. We reduced the strength of all harmonic constraints by a half every 0.1 ps, 10 times. Subsequently, constraints were set to 0. Finally, the system was equilibrated without constraints at 310K in the NPT ensemble for 1ns. For all production and equilibration simulations, a Langevin thermostat was employed with a 2fs timestep together with a friction coefficient of 1/picosecond to simulate the dynamics of the system.