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RNA. 1999 Nov; 5(11): 1458–1469.
PMCID: PMC1369867

Predicting oligonucleotide affinity to nucleic acid targets.


A computer program, OligoWalk, is reported that predicts the equilibrium affinity of complementary DNA or RNA oligonucleotides to an RNA target. This program considers the predicted stability of the oligonucleotide-target helix and the competition with predicted secondary structure of both the target and the oligonucleotide. Both unimolecular and bimolecular oligonucleotide self structure are considered with a user-defined concentration. The application of OligoWalk is illustrated with three comparisons to experimental results drawn from the literature.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Banerjee AR, Jaeger JA, Turner DH. Thermal unfolding of a group I ribozyme: the low-temperature transition is primarily disruption of tertiary structure. Biochemistry. 1993 Jan 12;32(1):153–163. [PubMed]
  • Bennett CF, Condon TP, Grimm S, Chan H, Chiang MY. Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. J Immunol. 1994 Apr 1;152(7):3530–3540. [PubMed]
  • Bevilacqua PC, Turner DH. Comparison of binding of mixed ribose-deoxyribose analogues of CUCU to a ribozyme and to GGAGAA by equilibrium dialysis: evidence for ribozyme specific interactions with 2' OH groups. Biochemistry. 1991 Nov 5;30(44):10632–10640. [PubMed]
  • Birikh KR, Berlin YA, Soreq H, Eckstein F. Probing accessible sites for ribozymes on human acetylcholinesterase RNA. RNA. 1997 Apr;3(4):429–437. [PMC free article] [PubMed]
  • Chang KY, Tinoco I., Jr Characterization of a "kissing" hairpin complex derived from the human immunodeficiency virus genome. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8705–8709. [PMC free article] [PubMed]
  • Chang KY, Tinoco I., Jr The structure of an RNA "kissing" hairpin complex of the HIV TAR hairpin loop and its complement. J Mol Biol. 1997 May 30;269(1):52–66. [PubMed]
  • Chiang MY, Chan H, Zounes MA, Freier SM, Lima WF, Bennett CF. Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem. 1991 Sep 25;266(27):18162–18171. [PubMed]
  • Comolli LR, Pelton JG, Tinoco I., Jr Mapping of a protein-RNA kissing hairpin interface: Rom and Tar-Tar*. Nucleic Acids Res. 1998 Oct 15;26(20):4688–4695. [PMC free article] [PubMed]
  • Crothers DM, Cole PE, Hilbers CW, Shulman RG. The molecular mechanism of thermal unfolding of Escherichia coli formylmethionine transfer RNA. J Mol Biol. 1974 Jul 25;87(1):63–88. [PubMed]
  • Lefebvre d'Hellencourt C, Diaw L, Cornillet P, Guenounou M. Inhibition of human TNF alpha and LT in cell-free extracts and in cell culture by antisense oligonucleotides. Biochim Biophys Acta. 1996 Dec 16;1317(3):168–174. [PubMed]
  • Dean NM, McKay R, Condon TP, Bennett CF. Inhibition of protein kinase C-alpha expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters. J Biol Chem. 1994 Jun 10;269(23):16416–16424. [PubMed]
  • Duff JL, Monia BP, Berk BC. Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. Effect of actinomycin D and antisense oligonucleotides. J Biol Chem. 1995 Mar 31;270(13):7161–7166. [PubMed]
  • Ehresmann C, Baudin F, Mougel M, Romby P, Ebel JP, Ehresmann B. Probing the structure of RNAs in solution. Nucleic Acids Res. 1987 Nov 25;15(22):9109–9128. [PMC free article] [PubMed]
  • Freier SM, Altmann KH. The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes. Nucleic Acids Res. 1997 Nov 15;25(22):4429–4443. [PMC free article] [PubMed]
  • Freier SM, Kierzek R, Caruthers MH, Neilson T, Turner DH. Free energy contributions of G.U and other terminal mismatches to helix stability. Biochemistry. 1986 Jun 3;25(11):3209–3213. [PubMed]
  • Gregorian RS, Jr, Crothers DM. Determinants of RNA hairpin loop-loop complex stability. J Mol Biol. 1995 May 19;248(5):968–984. [PubMed]
  • Hilbers CW, Robillard GT, Shulamn RG, Blake RD, Webb PK, Fresco R, Riesner D. Thermal unfolding of yeast glycine transfer RNA. Biochemistry. 1976 May 4;15(9):1874–1882. [PubMed]
  • Ho SP, Bao Y, Lesher T, Malhotra R, Ma LY, Fluharty SJ, Sakai RR. Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries. Nat Biotechnol. 1998 Jan;16(1):59–63. [PubMed]
  • Ho SP, Britton DH, Stone BA, Behrens DL, Leffet LM, Hobbs FW, Miller JA, Trainor GL. Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries. Nucleic Acids Res. 1996 May 15;24(10):1901–1907. [PMC free article] [PubMed]
  • Jaeger L, Westhof E, Michel F. Monitoring of the cooperative unfolding of the sunY group I intron of bacteriophage T4. The active form of the sunY ribozyme is stabilized by multiple interactions with 3' terminal intron components. J Mol Biol. 1993 Nov 20;234(2):331–346. [PubMed]
  • James BD, Olsen GJ, Pace NR. Phylogenetic comparative analysis of RNA secondary structure. Methods Enzymol. 1989;180:227–239. [PubMed]
  • Knapp G. Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods Enzymol. 1989;180:192–212. [PubMed]
  • Lan N, Howrey RP, Lee SW, Smith CA, Sullenger BA. Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. Science. 1998 Jun 5;280(5369):1593–1596. [PubMed]
  • Lee CH, Chen HH, Hoke G, Jong JS, White L, Kang YH. Antisense gene suppression against human ICAM-1, ELAM-1, and VCAM-1 in cultured human umbilical vein endothelial cells. Shock. 1995 Jul;4(1):1–10. [PubMed]
  • Lima WF, Brown-Driver V, Fox M, Hanecak R, Bruice TW. Combinatorial screening and rational optimization for hybridization to folded hepatitis C virus RNA of oligonucleotides with biological antisense activity. J Biol Chem. 1997 Jan 3;272(1):626–638. [PubMed]
  • Mathews DH, Banerjee AR, Luan DD, Eickbush TH, Turner DH. Secondary structure model of the RNA recognized by the reverse transcriptase from the R2 retrotransposable element. RNA. 1997 Jan;3(1):1–16. [PMC free article] [PubMed]
  • Mathews DH, Sabina J, Zuker M, Turner DH. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol. 1999 May 21;288(5):911–940. [PubMed]
  • Matveeva O, Felden B, Audlin S, Gesteland RF, Atkins JF. A rapid in vitro method for obtaining RNA accessibility patterns for complementary DNA probes: correlation with an intracellular pattern and known RNA structures. Nucleic Acids Res. 1997 Dec 15;25(24):5010–5016. [PMC free article] [PubMed]
  • Matveeva O, Felden B, Tsodikov A, Johnston J, Monia BP, Atkins JF, Gesteland RF, Freier SM. Prediction of antisense oligonucleotide efficacy by in vitro methods. Nat Biotechnol. 1998 Dec;16(13):1374–1375. [PubMed]
  • Milner N, Mir KU, Southern EM. Selecting effective antisense reagents on combinatorial oligonucleotide arrays. Nat Biotechnol. 1997 Jun;15(6):537–541. [PubMed]
  • Miraglia L, Geiger T, Bennett CF, Dean NM. Inhibition of interleukin-1 type I receptor expression in human cell-lines by an antisense phosphorothioate oligodeoxynucleotide. Int J Immunopharmacol. 1996 Apr;18(4):227–240. [PubMed]
  • Peyret N, Seneviratne PA, Allawi HT, SantaLucia J., Jr Nearest-neighbor thermodynamics and NMR of DNA sequences with internal A.A, C.C, G.G, and T.T mismatches. Biochemistry. 1999 Mar 23;38(12):3468–3477. [PubMed]
  • Pyle AM, Cech TR. Ribozyme recognition of RNA by tertiary interactions with specific ribose 2'-OH groups. Nature. 1991 Apr 18;350(6319):628–631. [PubMed]
  • Rivas E, Eddy SR. A dynamic programming algorithm for RNA structure prediction including pseudoknots. J Mol Biol. 1999 Feb 5;285(5):2053–2068. [PubMed]
  • Rychlik W, Rhoads RE. A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA. Nucleic Acids Res. 1989 Nov 11;17(21):8543–8551. [PMC free article] [PubMed]
  • SantaLucia J., Jr A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1460–1465. [PMC free article] [PubMed]
  • Allawi HT, SantaLucia J., Jr Thermodynamics and NMR of internal G.T mismatches in DNA. Biochemistry. 1997 Aug 26;36(34):10581–10594. [PubMed]
  • SantaLucia J, Jr, Allawi HT, Seneviratne PA. Improved nearest-neighbor parameters for predicting DNA duplex stability. Biochemistry. 1996 Mar 19;35(11):3555–3562. [PubMed]
  • Stepkowski SM, Tu Y, Condon TP, Bennett CF. Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities. J Immunol. 1994 Dec 1;153(11):5336–5346. [PubMed]
  • Stewart AJ, Canitrot Y, Baracchini E, Dean NM, Deeley RG, Cole SP. Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides. Biochem Pharmacol. 1996 Feb 23;51(4):461–469. [PubMed]
  • Strobel SA, Cech TR. Minor groove recognition of the conserved G.U pair at the Tetrahymena ribozyme reaction site. Science. 1995 Feb 3;267(5198):675–679. [PubMed]
  • Stull RA, Taylor LA, Szoka FC., Jr Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices. Nucleic Acids Res. 1992 Jul 11;20(13):3501–3508. [PMC free article] [PubMed]
  • Sugimoto N, Nakano S, Katoh M, Matsumura A, Nakamuta H, Ohmichi T, Yoneyama M, Sasaki M. Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes. Biochemistry. 1995 Sep 5;34(35):11211–11216. [PubMed]
  • Testa SM, Gryaznov SM, Turner DH. Antisense binding enhanced by tertiary interactions: binding of phosphorothioate and N3'-->P5' phosphoramidate hexanucleotides to the catalytic core of a group I ribozyme from the mammalian pathogen Pneumocystis carinii. Biochemistry. 1998 Jun 30;37(26):9379–9385. [PubMed]
  • Testa SM, Haidaris CG, Gigliotti F, Turner DH. A Pneumocystis carinii group I intron ribozyme that does not require 2' OH groups on its 5' exon mimic for binding to the catalytic core. Biochemistry. 1997 Dec 9;36(49):15303–15314. [PubMed]
  • Tu GC, Cao QN, Zhou F, Israel Y. Tetranucleotide GGGA motif in primary RNA transcripts. Novel target site for antisense design. J Biol Chem. 1998 Sep 25;273(39):25125–25131. [PubMed]
  • Xia T, SantaLucia J, Jr, Burkard ME, Kierzek R, Schroeder SJ, Jiao X, Cox C, Turner DH. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs. Biochemistry. 1998 Oct 20;37(42):14719–14735. [PubMed]
  • Zarrinkar PP, Williamson JR. Kinetic intermediates in RNA folding. Science. 1994 Aug 12;265(5174):918–924. [PubMed]
  • Zuker M. On finding all suboptimal foldings of an RNA molecule. Science. 1989 Apr 7;244(4900):48–52. [PubMed]
  • Zuker M, Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. [PMC free article] [PubMed]

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