Sequence determines the structure, and the structure in turn determines the function, are the fundamental principles of protein chemistry. In the genomics era, the paradigm of mining protein functionality and evolutionary insights through sequence analysis has led to remarkable achievements. However, protein sequences often mutate faster than their structural counterparts during evolution. For protein sets characterized by highly divergent sequences, sequence-based analysis is often inadequate, whereas direct extraction of implicit information from the structures appears to be a more effective strategy.