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. 1997 Nov 1;25(21):4408–4415. doi: 10.1093/nar/25.21.4408

Sequence walkers: a graphical method to display how binding proteins interact with DNA or RNA sequences.

T D Schneider 1
PMCID: PMC147041  PMID: 9336476

Abstract

A graphical method is presented for displaying how binding proteins and other macromolecules interact with individual bases of nucleotide sequences. Characters representing the sequence are either oriented normally and placed above a line indicating favorable contact, or upside-down and placed below the line indicating unfavorable contact. The positive or negative height of each letter shows the contribution of that base to the average sequence conservation of the binding site, as represented by a sequence logo. These sequence 'walkers' can be stepped along raw sequence data to visually search for binding sites. Many walkers, for the same or different proteins, can be simultaneously placed next to a sequence to create a quantitative map of a complex genetic region. One can alter the sequence to quantitatively engineer binding sites. Database anomalies can be visualized by placing a walker at the recorded positions of a binding molecule and by comparing this to locations found by scanning the nearby sequences. The sequence can also be altered to predict whether a change is a polymorphism or a mutation for the recognizer being modeled.

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Selected References

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  1. Ball C. A., Johnson R. C. Efficient excision of phage lambda from the Escherichia coli chromosome requires the Fis protein. J Bacteriol. 1991 Jul;173(13):4027–4031. doi: 10.1128/jb.173.13.4027-4031.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball C. A., Johnson R. C. Multiple effects of Fis on integration and the control of lysogeny in phage lambda. J Bacteriol. 1991 Jul;173(13):4032–4038. doi: 10.1128/jb.173.13.4032-4038.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blom N., Hansen J., Blaas D., Brunak S. Cleavage site analysis in picornaviral polyproteins: discovering cellular targets by neural networks. Protein Sci. 1996 Nov;5(11):2203–2216. doi: 10.1002/pro.5560051107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Finkel S. E., Johnson R. C. The Fis protein: it's not just for DNA inversion anymore. Mol Microbiol. 1992 Nov;6(22):3257–3265. doi: 10.1111/j.1365-2958.1992.tb02193.x. [DOI] [PubMed] [Google Scholar]
  5. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  6. Goodrich J. A., Schwartz M. L., McClure W. R. Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF). Nucleic Acids Res. 1990 Sep 11;18(17):4993–5000. doi: 10.1093/nar/18.17.4993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hübner P., Arber W. Mutational analysis of a prokaryotic recombinational enhancer element with two functions. EMBO J. 1989 Feb;8(2):577–585. doi: 10.1002/j.1460-2075.1989.tb03412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Landy A. Dynamic, structural, and regulatory aspects of lambda site-specific recombination. Annu Rev Biochem. 1989;58:913–949. doi: 10.1146/annurev.bi.58.070189.004405. [DOI] [PubMed] [Google Scholar]
  9. Landy A., Ross W. Viral integration and excision: structure of the lambda att sites. Science. 1977 Sep 16;197(4309):1147–1160. doi: 10.1126/science.331474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
  11. Numrych T. E., Gumport R. I., Gardner J. F. Characterization of the bacteriophage lambda excisionase (Xis) protein: the C-terminus is required for Xis-integrase cooperativity but not for DNA binding. EMBO J. 1992 Oct;11(10):3797–3806. doi: 10.1002/j.1460-2075.1992.tb05465.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Papp P. P., Chattoraj D. K., Schneider T. D. Information analysis of sequences that bind the replication initiator RepA. J Mol Biol. 1993 Sep 20;233(2):219–230. doi: 10.1006/jmbi.1993.1501. [DOI] [PubMed] [Google Scholar]
  13. Papp P. P., Iyer V. N. Determination of the binding sites of RepA, a replication initiator protein of the basic replicon of the IncN group plasmid pCU1. J Mol Biol. 1995 Mar 10;246(5):595–608. doi: 10.1016/s0022-2836(05)80109-3. [DOI] [PubMed] [Google Scholar]
  14. Pietrokovski S., Henikoff J. G., Henikoff S. The Blocks database--a system for protein classification. Nucleic Acids Res. 1996 Jan 1;24(1):197–200. doi: 10.1093/nar/24.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pietrokovski S. Searching databases of conserved sequence regions by aligning protein multiple-alignments. Nucleic Acids Res. 1996 Oct 1;24(19):3836–3845. doi: 10.1093/nar/24.19.3836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rogan P. K., Schneider T. D. Using information content and base frequencies to distinguish mutations from genetic polymorphisms in splice junction recognition sites. Hum Mutat. 1995;6(1):74–76. doi: 10.1002/humu.1380060114. [DOI] [PubMed] [Google Scholar]
  17. Sanger F., Coulson A. R., Hong G. F., Hill D. F., Petersen G. B. Nucleotide sequence of bacteriophage lambda DNA. J Mol Biol. 1982 Dec 25;162(4):729–773. doi: 10.1016/0022-2836(82)90546-0. [DOI] [PubMed] [Google Scholar]
  18. Schneider T. D. Reading of DNA sequence logos: prediction of major groove binding by information theory. Methods Enzymol. 1996;274:445–455. doi: 10.1016/s0076-6879(96)74036-3. [DOI] [PubMed] [Google Scholar]
  19. Schneider T. D., Stephens R. M. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res. 1990 Oct 25;18(20):6097–6100. doi: 10.1093/nar/18.20.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schneider T. D., Stormo G. D., Gold L., Ehrenfeucht A. Information content of binding sites on nucleotide sequences. J Mol Biol. 1986 Apr 5;188(3):415–431. doi: 10.1016/0022-2836(86)90165-8. [DOI] [PubMed] [Google Scholar]
  21. Schneider T. D., Stormo G. D., Haemer J. S., Gold L. A design for computer nucleic-acid-sequence storage, retrieval, and manipulation. Nucleic Acids Res. 1982 May 11;10(9):3013–3024. doi: 10.1093/nar/10.9.3013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schneider T. D., Stormo G. D., Yarus M. A., Gold L. Delila system tools. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):129–140. doi: 10.1093/nar/12.1part1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schneider T. D. Theory of molecular machines. I. Channel capacity of molecular machines. J Theor Biol. 1991 Jan 7;148(1):83–123. doi: 10.1016/s0022-5193(05)80466-7. [DOI] [PubMed] [Google Scholar]
  24. Schneider T. D. Theory of molecular machines. II. Energy dissipation from molecular machines. J Theor Biol. 1991 Jan 7;148(1):125–137. doi: 10.1016/s0022-5193(05)80467-9. [DOI] [PubMed] [Google Scholar]
  25. Slany R. K., Kersten H. The promoter of the tgt/sec operon in Escherichia coli is preceded by an upstream activation sequence that contains a high affinity FIS binding site. Nucleic Acids Res. 1992 Aug 25;20(16):4193–4198. doi: 10.1093/nar/20.16.4193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Staden R. Computer methods to locate signals in nucleic acid sequences. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):505–519. doi: 10.1093/nar/12.1part2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stephens R. M., Schneider T. D. Features of spliceosome evolution and function inferred from an analysis of the information at human splice sites. J Mol Biol. 1992 Dec 20;228(4):1124–1136. doi: 10.1016/0022-2836(92)90320-j. [DOI] [PubMed] [Google Scholar]
  28. Stormo G. D. Consensus patterns in DNA. Methods Enzymol. 1990;183:211–221. doi: 10.1016/0076-6879(90)83015-2. [DOI] [PubMed] [Google Scholar]
  29. Stormo G. D., Schneider T. D., Gold L., Ehrenfeucht A. Use of the 'Perceptron' algorithm to distinguish translational initiation sites in E. coli. Nucleic Acids Res. 1982 May 11;10(9):2997–3011. doi: 10.1093/nar/10.9.2997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stormo G. D., Schneider T. D., Gold L. Quantitative analysis of the relationship between nucleotide sequence and functional activity. Nucleic Acids Res. 1986 Aug 26;14(16):6661–6679. doi: 10.1093/nar/14.16.6661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson J. F., Moitoso de Vargas L., Koch C., Kahmann R., Landy A. Cellular factors couple recombination with growth phase: characterization of a new component in the lambda site-specific recombination pathway. Cell. 1987 Sep 11;50(6):901–908. doi: 10.1016/0092-8674(87)90516-2. [DOI] [PubMed] [Google Scholar]

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