Correlated mutations: Advances and limitations. A study on fusion proteins and on the Cohesin-Dockerin families

Inbal Halperin, Haim Wolfson, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Correlated mutations have been repeatedly exploited for intramolecular contact map prediction. Over the last decade these efforts yielded several methods for measuring correlated mutations. Nevertheless, the application of correlated mutations for the prediction of intermolecular interactions has not yet been explored. This gap is due to several obstacles, such as 3D complexes availability, paralog discrimination, and the availability of sequence pairs that are required for inter- but not intramolecular analyses. Here we selected for analysis fusion protein families that bypass some of these obstacles. We find that several correlated mutation measurements yield reasonable accuracy for intramolecular contact map prediction on the fusion dataset. However, the accuracy level drops sharply in intermolecular contacts prediction. This drop in accuracy does not occmr always. In the Cohesin-Dockerin family, reasonable accuracy is achieved in the prediction of both intra- and intermolecular contacts. The Cohesin-Dockerin family is well suited for correlated mutation analysis. Because, however, this family constitutes a special case (it has radical mutations, has domain repeats, within each species each Dockerin domain interacts with each Cohesin domain, see below), the successful prediction in this family does not point to a general potential in using correlated mutations for predicting intermolecular contacts. Overall, the results of our study indicate that current methodologies of correlated mutations analysis are not suitable for large-scale intermolecular contact prediction, and thus cannot assist in docking. With current measurements, sequence availability, sequence annotations, and underdeveloped sequence pairing methods, correlated mutations can yield reasonable accuracy only for a handful of families.

Original languageEnglish
Pages (from-to)832-845
Number of pages14
JournalProteins: Structure, Function and Genetics
Issue number4
StatePublished - 1 Jun 2006


  • Binding site
  • Correlated mutations
  • Fusion proteins
  • Protein-protein interactions
  • Residue covariation


Dive into the research topics of 'Correlated mutations: Advances and limitations. A study on fusion proteins and on the Cohesin-Dockerin families'. Together they form a unique fingerprint.

Cite this