Understanding protein–ligand molecular interactions is fundamental to understanding the role of proteins in complex diseases such as cancer. For instance, from a structural computational biology standpoint, there is growing interest in predicting the binding modes of peptide-based ligands (e.g., cyclic and phosphorylated peptides) to inhibit or induce targeted degradation of high-profile cancer targets. Focusing on structural immunoinformatics, another promising example is the identification of tumor-associated antigens for cancer immunotherapy applications. Both examples involve very specific molecular interactions, provide opportunities for computer-aided design of better cancer treatments, and highlight the need for structural analyses in cancer research. They also require new methods that account for the flexibility and variability of the protein receptors involved in these molecular interactions.