Identifying interaction sites in "Recalcitrant" proteins: Predicted protein and RNA binding sites in REV proteins of HIV-1 and EIAV agree with experimental data

Michael Terribllini, Jae Hyung Lee, Changhui Yan, Robert L. Jernigan, Susan Carpenter, Vasant Honavar, Drena Dobbs

Research output: Chapter in Book/Report/Conference proceedingConference contribution

9 Scopus citations

Abstract

Protein-protein and protein nucleic acid interactions are vitally important for a wide range of biological processes, including regulation or gene expression, protein synthesis, and replication and assembly of many viruses. We have developed machine learning approaches for predicting which amino acids of a protein participate in its interactions with other proteins and/or nucleic acids, using only the proiein sequence as input. In this paper, we describe an application of classifiers trained on datasets of well-characterized protein-protein and protein-RNA complexes for which experimental structures are available. We apply these classifiers to the problem of predicting protein and RNA binding sites in the sequence of a clinically important protein for which the structure is not known: the regulatory protein Rev, essential for the replication of HIV-I and other lentiviruses. We compare our predictions with published biochemical, genetic and partial structural information for HIV-1 and EIAV Rev and with our own published experimental mapping of RNA binding sites in EIAV Rev. The predicted and experimentally determined binding sites are in very good agreement. The ability to predict reliably the residues of a protein that directly contribute to specific binding events - without the requirement for structural information regarding either the protein or complexes in which it participates - can potentially generate new disease intervention strategies.

Original languageEnglish (US)
Title of host publicationProceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006
Pages415-426
Number of pages12
Publication statusPublished - Dec 1 2006
Event11th Pacific Symposium on Biocomputing 2006, PSB 2006 - Maui, HI, United States
Duration: Jan 3 2006Jan 7 2006

Publication series

NameProceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006

Other

Other11th Pacific Symposium on Biocomputing 2006, PSB 2006
CountryUnited States
CityMaui, HI
Period1/3/061/7/06

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Computational Theory and Mathematics
  • Biomedical Engineering
  • Medicine(all)

Cite this

Terribllini, M., Lee, J. H., Yan, C., Jernigan, R. L., Carpenter, S., Honavar, V., & Dobbs, D. (2006). Identifying interaction sites in "Recalcitrant" proteins: Predicted protein and RNA binding sites in REV proteins of HIV-1 and EIAV agree with experimental data. In Proceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006 (pp. 415-426). (Proceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006).