In gentle ensemble refinement, we demand that S KL ≲ 1, S KL (p||q) ≈ S KL (q||p), and S KL ≈ var(β∆U )/2 according to Eq. ( ). For a given force-field error, we then expect SKL ≈ var(β∆U )/2. According to Eq. ( ), we set θ ∼ = 2/var(β∆U ) a priori as in Eq. ( ). Beyond gentle ensemble refinement, where the expectation of the KL divergence is no longer determined by var(β∆U ), we have to set SKL directly to encode our prior knowledge.