Journal of Molecular Modeling

, Volume 12, Issue 6, pp 921–929 | Cite as

Determining functionally important amino acid residues of the E1 protein of Venezuelan equine encephalitis virus

  • Surendra S. Negi
  • Andrey A. Kolokoltsov
  • Catherine H. Schein
  • Robert A. Davey
  • Werner BraunEmail author
Original paper


A new method for predicting interacting residues in protein complexes, InterProSurf, was applied to the E1 envelope protein of Venezuelan equine encephalitis (VEEV). Monomeric and trimeric models of VEEV-E1 were constructed with our MPACK program, using the crystal structure of the E1 protein of Semliki forest virus as a template. An alignment of the E1 sequences from representative alphavirus sequences was used to determine physical chemical property motifs (likely functional areas) with our PCPMer program. Information on residue variability, propensity to be in protein interfaces, and surface exposure on the model was combined to predict surface clusters likely to interact with other viral or cellular proteins. Mutagenesis of these clusters indicated that the predictions accurately detected areas crucial for virus infection. In addition to the fusion peptide area in domain 2, at least two other surface areas play an important role in virus infection. We propose that these may be sites of interaction between the E1–E1 and E1–E2 subdomains of the envelope proteins that are required to assemble the functional unit. The InterProSurf method is, thus, an important new tool for predicting viral protein interactions. These results can aid in the design of new vaccines against alphaviruses and other viruses.

D model of the E1 protein of VEEV showing a comparison of interface residues (green) predicted by InterProSurf (left view) and residues showing the experimental effect of mutations on the titer of pseudotyped MLV particles with red most dramatic changes and blue as wild type


Venezuelan equine encephalitis virus (VEEV) Alpha virus Protein–protein interaction Envelope glycoprotein Functional site prediction 



We thank Dr. Numan Oezguen and Dr. Bin Zhou for fruitful discussions and help in drawing the amino acid residue variability plot. This project was supported by NIH grant No. R21 AI055746.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Surendra S. Negi
    • 1
  • Andrey A. Kolokoltsov
    • 2
  • Catherine H. Schein
    • 1
  • Robert A. Davey
    • 2
  • Werner Braun
    • 1
    • 3
    Email author
  1. 1.Sealy Center for Structural Biology, Department of Biochemistry and Molecular BiologyUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Department of Microbiology and ImmunologyUniversity of Texas Medical BranchGalvestonUSA
  3. 3.University of Texas Medical BranchGalvestonUSA

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