For the MALT1 system, we used PDB 7AK1 as the input structure since the ligand in that crystal structure was similar to the ligands in this study. We prepared the protein using OpenEye Spruce (Orion floe "SPRUCE -Protein Preparation from PDB Codes"). Missing loops were built and crystallographic waters were retained. The 16 ligands were then aligned onto the crystallographic ligand using Open-Eye's ShapeFit method 49,50 as implemented in the SystemBuilder package. Similarly as described above, Orion floes "Bound Protein-Ligand MD" for the protein-ligand complex and "Solvate and Run MD" for the unbound ligands were used to solvate and parameterize the systems. The Open Force Field version 1.3.1 and AM1-BCC charges were used for the ligands, Amber ff14SB for the protein, and TIP3P 44 for the water.