title: The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis.
abstract: 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 [http://hivtoolbox2.bio-toolkit.com].
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: David P
authors.initials: DP
authors.lastname: Sargeant
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Deverasetty
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Strong
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Izua J
authors.initials: IJ
authors.lastname: Alaniz
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Bartlett
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Brandon
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Brooks
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Brown
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Flaviona
authors.initials: F
authors.lastname: Bufi
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Monika
authors.initials: M
authors.lastname: Chakarova
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Roxanne P
authors.initials: RP
authors.lastname: David
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Karlyn M
authors.initials: KM
authors.lastname: Dobritch
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Horacio P
authors.initials: HP
authors.lastname: Guerra
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Hedden
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Rma
authors.initials: R
authors.lastname: Kumra
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Kelvy S
authors.initials: KS
authors.lastname: Levitt
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Kiran R
authors.initials: KR
authors.lastname: Mathew
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Ray
authors.initials: R
authors.lastname: Matti
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Dorothea Q
authors.initials: DQ
authors.lastname: Maza
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Sabyasachy
authors.initials: S
authors.lastname: Mistry
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Novakovic
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Austin
authors.initials: A
authors.lastname: Pomerantz
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Josue
authors.initials: J
authors.lastname: Portillo
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Rafalski
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Viraj R
authors.initials: VR
authors.lastname: Rathnayake
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Noura
authors.initials: N
authors.lastname: Rezapour
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Songao
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Tuggle
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Sandy
authors.initials: S
authors.lastname: Yousif
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: David I
authors.initials: DI
authors.lastname: Dorsky
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Schiller
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D024882:Drug Resistance, Viral / Q000235:genetics*; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020407:Internet; D009154:Mutation; D011487:Protein Conformation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D020539:Sequence Analysis, Protein; D012984:Software
chemical_list: D019380:Anti-HIV Agents; D054298:Human Immunodeficiency Virus Proteins