is the unnormalized weight for configuration r n under U 0 (r). To ameliorate the numerical instability originated from incomplete sampling, the weights ω t (r n ) under the target Hamiltonian are scaled by Gaussian-smoothing on the density-of-states. In this work, we take U 0 as the PM6/MM 54 Hamiltonian, and U t as the BLYP-D3/6-31G(d)/MM 55-57 level of theory. For simplicity, they will be labeled as the SQM and DFT level of theories. Please also note that η is unnecessarily ξ, but we set them equal in this work.