Using property based sequence motifs and 3D modeling to determine structure and functional regions of proteins

Ovidiu Ivanciuc, Numan Oezguen, Venkatarajan S. Mathura, Catherine H. Schein, Yuan Xu, Werner Braun

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Homology modeling has become an essential tool for studying proteins that are targets for medical drug design. This paper describes the approach we developed that combines sequence decomposition techniques with distance geometry algorithms for homology modeling to determine functionally important regions of proteins. We show here the application of these techniques to targets of medical interest chosen from those included in the CASP5 (Critical Assessment of Techniques for Protein Structure Prediction) competition, including the dihydroneopterin aldolase from Mycobacterium tuberculosis, RNase III of Thermobacteria maritima, and the NO-transporter nitrophorin from saliva of the bedbug Cimex lectularius. Physical chemical property (PCP) motifs, identified in aligned sequences with our MASIA program, can be used to select among different alignments returned by fold recognition servers. They can also be used to suggest functions for hypothetical proteins, as we illustrate for target T188. Once a suitable alignment has been made with the template, our modeling suite MPACK generates a series of possible models. The models can then be selected according to their match in areas known to be conserved in protein families. Alignments based on motifs can improve the structural matching of residues in the active site. The quality of the local structure of our 3D models near active sites or epitopes makes them useful aids for drug and vaccine design. Further, the PCP motif approach, when combined with a structural filter, can be a potent way to detect areas involved in activity and to suggest function for novel genome sequences.

Original languageEnglish (US)
Pages (from-to)583-593
Number of pages11
JournalCurrent Medicinal Chemistry
Volume11
Issue number5
DOIs
StatePublished - Mar 2004

Fingerprint

Bedbugs
dihydroneopterin aldolase
Drug Design
Proteins
Chemical properties
Catalytic Domain
Ribonuclease III
Saliva
Mycobacterium tuberculosis
Pharmaceutical Preparations
Epitopes
Servers
Vaccines
Genes
Genome
Decomposition
Geometry

Keywords

  • Bayesian statistics
  • CASP5
  • Drug and vaccine design
  • Functional annotation
  • MASIA
  • PCPMer
  • Physical-chemical properties
  • Sequence motifs

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Using property based sequence motifs and 3D modeling to determine structure and functional regions of proteins. / Ivanciuc, Ovidiu; Oezguen, Numan; Mathura, Venkatarajan S.; Schein, Catherine H.; Xu, Yuan; Braun, Werner.

In: Current Medicinal Chemistry, Vol. 11, No. 5, 03.2004, p. 583-593.

Research output: Contribution to journalArticle

Ivanciuc, Ovidiu ; Oezguen, Numan ; Mathura, Venkatarajan S. ; Schein, Catherine H. ; Xu, Yuan ; Braun, Werner. / Using property based sequence motifs and 3D modeling to determine structure and functional regions of proteins. In: Current Medicinal Chemistry. 2004 ; Vol. 11, No. 5. pp. 583-593.
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