Fig. 2. QM/MM umbrella sampling of the proton transfer in the catalytic dyad. Representation of the interactions of the Cys-145 thiolate in the ion pair (IP) state from the (a) forwards and (b) backwards simulations. (c) Free energy profile for interconversion of the neutral (N) and ion pair states of the dyad in the HIE-163 system, from the combined forwards and backwards QM/MM umbrella sampling MD simulations, corrected to the ωB97X-D/6-31G(d)/MM level of theory.
