Structure-based drug design (SBDD) is commonly leveraged in rational drug design. Usually, ligand and binding site atomic coordinates from crystallographic data are exploited to optimize potency and selectivity. In addition to traditional, static views of proteins and ligands, we propose using normalized B-factors to study protein dynamics as a part of the drug optimization process. A retrospective case study of crizotinib and lorlatinib bound to both c-ros oncogene 1 kinase (ROS1) and anaplastic lymphoma kinase (ALK) L1196M related normalized B-factors to differences in binding affinity. This analysis showed that ligand binding can have protein-stabilizing effects that start near the ligand but propagate through nearby residues and structural waters to more distal motifs. The potential opportunities for analyzing normalized B-factors in SBDD are also discussed.