The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis

PLoS One. 2014 Jun 2;9(6):e98810. doi: 10.1371/journal.pone.0098810. eCollection 2014.


There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at [].

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemistry*
  • Binding Sites / genetics
  • DNA Mutational Analysis
  • Databases, Genetic
  • Drug Resistance, Viral / genetics*
  • HIV / drug effects*
  • HIV / genetics
  • HIV / metabolism
  • Human Immunodeficiency Virus Proteins / chemistry*
  • Human Immunodeficiency Virus Proteins / drug effects
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Internet
  • Mutation*
  • Protein Conformation
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Sequence Analysis, Protein
  • Software*


  • Anti-HIV Agents
  • Human Immunodeficiency Virus Proteins