Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals.

Catherine H. Schein, David M. Bowen, Jessica A. Lewis, Kyung Choi, Aniko Paul, Gerbrand J. van der Heden van Noort, Wenzhe Lu, Dmitri V. Filippov

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Analysis of large sets of biological sequence data from related strains or organisms is complicated by superficial redundancy in the set, which may contain many members that are identical except at one or two positions. Thus a new method, based on deriving physicochemical property (PCP)-consensus sequences, was tested for its ability to generate reference sequences and distinguish functionally significant changes from background variability. The PCP consensus program was used to automatically derive consensus sequences starting from sequence alignments of proteins from Flaviviruses (from the Flavitrack database) and human enteroviruses, using a five dimensional set of Eigenvectors that summarize over 200 different scalar values for the PCPs of the amino acids. A PCP-consensus protein of a Dengue virus envelope protein was produced recombinantly and tested for its ability to bind antibodies to strains using ELISA. PCP-consensus sequences of the flavivirus family could be used to classify them into five discrete groups and distinguish areas of the envelope proteins that correlate with host specificity and disease type. A multivalent Dengue virus antigen was designed and shown to bind antibodies against all four DENV types. A consensus enteroviral VPg protein had the same distinctive high pKa as wild type proteins and was recognized by two different polymerases. The process for deriving PCP-consensus sequences for any group of aligned similar sequences, has been validated for sequences with up to 50% diversity. Ongoing projects have shown that the method identifies residues that significantly alter PCPs at a given position, and might thus cause changes in function or immunogenicity. Other potential applications include deriving target proteins for drug design and diagnostic kits.

Original languageEnglish (US)
JournalBMC Bioinformatics
Volume13 Suppl 13
StatePublished - 2012
Externally publishedYes

Fingerprint

Functional analysis
Consensus Sequence
Functional Analysis
Antigens
Antiviral Agents
Sequence Analysis
Proteins
Protein
Flavivirus
Dengue Virus
Viruses
Antibodies
Chemical Phenomena
Antibody
Envelope
Viral Envelope Proteins
Virus
Enterovirus
Sequence Alignment
Drug Design

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics
  • Structural Biology

Cite this

Schein, C. H., Bowen, D. M., Lewis, J. A., Choi, K., Paul, A., van der Heden van Noort, G. J., ... Filippov, D. V. (2012). Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals. BMC Bioinformatics, 13 Suppl 13.

Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals. / Schein, Catherine H.; Bowen, David M.; Lewis, Jessica A.; Choi, Kyung; Paul, Aniko; van der Heden van Noort, Gerbrand J.; Lu, Wenzhe; Filippov, Dmitri V.

In: BMC Bioinformatics, Vol. 13 Suppl 13, 2012.

Research output: Contribution to journalArticle

Schein, CH, Bowen, DM, Lewis, JA, Choi, K, Paul, A, van der Heden van Noort, GJ, Lu, W & Filippov, DV 2012, 'Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals.', BMC Bioinformatics, vol. 13 Suppl 13.
Schein, Catherine H. ; Bowen, David M. ; Lewis, Jessica A. ; Choi, Kyung ; Paul, Aniko ; van der Heden van Noort, Gerbrand J. ; Lu, Wenzhe ; Filippov, Dmitri V. / Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals. In: BMC Bioinformatics. 2012 ; Vol. 13 Suppl 13.
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