Modeling hybridization kinetics

Jian Ying Wang, Karl Drlica

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Formation of complementary base pairs between nucleic acids over a short region (≤ 15 nucleotides) is described by a kinetic model in which the intermediate state is assumed to be locally single stranded. The model enables calculation of a rate factor that is proportional to the rate constant for hybridization under steady-state reaction conditions. Rate factors calculated for various sites in acetylcholinesterase mRNA correlated with sites found previously to be experimentally accessible for hybridization to antisense oligonucleotides. Hybridization rate of longer antisense oligodeoxynucleotides was modeled by calculation of a maximal rate factor for all possible 15-nucleotide segments of a given antisense molecule. Maximal rate factor calculated for a set of antisense oligonucleotides correlated (r = 0.95) with initial rate of hybridization reported previously. Two other models proposed for identifying accessible sites for hybridization were less predictive than the rate factor calculation.

Original languageEnglish (US)
Pages (from-to)37-47
Number of pages11
JournalMathematical Biosciences
Volume183
Issue number1
DOIs
StatePublished - May 2003

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Keywords

  • Antisense
  • Hybridization kinetics
  • Hybridization rate
  • Hybridization thermodynamics
  • Inhibition
  • RNA target accessibility
  • Site selection

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