Discrimination between Distant Homologs and Structural Analogs: Lessons from Manually Constructed, Reliable Data Sets

Hua Cheng, Bong Hyun Kim, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


A natural way to study protein sequence, structure, and function is to put them in the context of evolution. Homologs inherit similarities from their common ancestor, while analogs converge to similar structures due to a limited number of energetically favorable ways to pack secondary structural elements. Using novel strategies, we previously assembled two reliable databases of homologs and analogs. In this study, we compare these two data sets and develop a support vector machine (SVM)-based classifier to discriminate between homologs and analogs. The classifier uses a number of well-known similarity scores. We observe that although both structure scores and sequence scores contribute to SVM performance, profile sequence scores computed based on structural alignments are the best discriminators between remote homologs and structural analogs. We apply our classifier to a representative set from the expert-constructed database, Structural Classification of Proteins (SCOP). The SVM classifier recovers 76% of the remote homologs defined as domains in the same SCOP superfamily but from different families. More importantly, we also detect and discuss interesting homologous relationships between SCOP domains from different superfamilies, folds, and even classes.

Original languageEnglish (US)
Pages (from-to)1265-1278
Number of pages14
JournalJournal of Molecular Biology
Issue number4
StatePublished - Apr 4 2008


  • analogy
  • discrimination
  • homology
  • protein structures
  • support vector machines

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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