To characterize mutations remote from catalytic sites (20 out of 24 known mutations), 40 independent microsecond-long MD simulations for each of the cancer-associated apo-SETD8 mutants were conducted with seed structures prepared from one ternary complex (TC) conformer---a structure resembling the enzymatic transition state and thus essential for SETD8-catalyzed methylation reaction (Linscott et al., 2016). Here, KMT5A is linked to cancer.