Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions

Te Lun Mai, Geng Ming Hu, Chi Ming Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Research in the recent decade has demonstrated the usefulness of protein network knowledge in furthering the study of molecular evolution of proteins, understanding the robustness of cells to perturbation, and annotating new protein functions. In this study, we aimed to provide a general clustering approach to visualize the sequence-structure-function relationship of protein networks, and investigate possible causes for inconsistency in the protein classifications based on sequences, structures, and functions. Such visualization of protein networks could facilitate our understanding of the overall relationship among proteins and help researchers comprehend various protein databases. As a demonstration, we clustered 1437 enzymes by their sequences and structures using the minimum span clustering (MSC) method. The general structure of this protein network was delineated at two clustering resolutions, and the second level MSC clustering was found to be highly similar to existing enzyme classifications. The clustering of these enzymes based on sequence, structure, and function information is consistent with each other. For proteases, the Jaccard's similarity coefficient is 0.86 between sequence and function classifications, 0.82 between sequence and structure classifications, and 0.78 between structure and function classifications. From our clustering results, we discussed possible examples of divergent evolution and convergent evolution of enzymes. Our clustering approach provides a panoramic view of the sequence-structure-function network of proteins, helps visualize the relation between related proteins intuitively, and is useful in predicting the structure and function of newly determined protein sequences.

Original languageEnglish
Pages (from-to)2123-2131
Number of pages9
JournalJournal of Proteome Research
Issue number7
Publication statusPublished - 2016 Jul 1


  • protein similarity networks
  • sequence similarity
  • sequence-structure-function relationship
  • structure similarity

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry


Dive into the research topics of 'Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions'. Together they form a unique fingerprint.

Cite this