(A) Selected 2D surface, harmonically restrained along the course-grained metal ion binding coordinate at d(Mg2+,G8:O2′) = 2.5Å, where z1 = d(O5′,P) - d(P,O2′), z2 = d(G8:O2′,H) - d(H,O5′). (B) 2D PMF for Mg2+ binding mode in phosphoryl transfer step, where z4 = d(Mg2+,O5′) + d(Mg2+,G8:O2′). (C) 2D PMF for Mg2+ binding mode in general acid step, where z5 = d(Mg2+,O5′) - d(Mg2+,G8:O2′). d(x,y) denotes distance between x and y. TS is the acronym of transition state.