Theoretical limits of DNA sequence discrimination of polyamides

Wynn L. Walker, David S. Goodsell, Elliot M. Landaw

Research output: Contribution to conferencePaper

Abstract

Linked polyamides bind in the minor groove of double-stranded DNA in a partially sequence-specific manner but have limited sequence discriminatory abilities, suggesting a need for design alternatives to create molecules with enhanced sequence selectivity. We present an analysis of the theoretical limits of the DNA sequence selectivity of hypothetical sequence reading molecules as a function of their base recognition properties and sequence content of their target sequence. The analysis shows the nonobvious result that molecules containing nonspecific readers at critical positions within the molecule may have enhanced sequence selectivity over molecules composed entirely of base specific reading elements. We apply this result to determine optimal patterns of base recognition for molecules in order to optimize their target sequence selectivity. We also examine the effect of the length of a polyamide (i.e. the number of base pairs it binds) on its sequence discriminatory ability and determine necessary concentration dependent constraints on the binding free energies in order for longer polyamides to have greater sequence specificity than shorter ones.

Original languageEnglish (US)
Pages270-275
Number of pages6
StatePublished - Jan 1 1998
Externally publishedYes
EventProceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology - New York, NY, USA
Duration: Mar 22 1998Mar 25 1998

Other

OtherProceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology
CityNew York, NY, USA
Period3/22/983/25/98

Fingerprint

DNA sequences
Nylons
Polyamides
Molecules
Reading
Base Pairing
DNA
Free energy

All Science Journal Classification (ASJC) codes

  • Computer Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Walker, W. L., Goodsell, D. S., & Landaw, E. M. (1998). Theoretical limits of DNA sequence discrimination of polyamides. 270-275. Paper presented at Proceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology, New York, NY, USA, .
Walker, Wynn L. ; Goodsell, David S. ; Landaw, Elliot M. / Theoretical limits of DNA sequence discrimination of polyamides. Paper presented at Proceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology, New York, NY, USA, .6 p.
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Walker, WL, Goodsell, DS & Landaw, EM 1998, 'Theoretical limits of DNA sequence discrimination of polyamides', Paper presented at Proceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology, New York, NY, USA, 3/22/98 - 3/25/98 pp. 270-275.

Theoretical limits of DNA sequence discrimination of polyamides. / Walker, Wynn L.; Goodsell, David S.; Landaw, Elliot M.

1998. 270-275 Paper presented at Proceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology, New York, NY, USA, .

Research output: Contribution to conferencePaper

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Walker WL, Goodsell DS, Landaw EM. Theoretical limits of DNA sequence discrimination of polyamides. 1998. Paper presented at Proceedings of the 1998 2nd Annual International Conference on Computational Molecular Biology, New York, NY, USA, .