A Non-Watson–Crick Motif of Base-pairing on Surfaces for Untethered Oligonucleotides

Abstract

A structural view of DNA association/hybridization to a target oligonucleotide molecule near a surface has been developed. Recent experiments have showed a kinetically rapid hybridization between large target DNA fragments and oligonucleotides electrostatically immobilized (untethered) to a surface. Theory and computer simulations have been used to investigate the nature of the specificity and affinity in such a system. Simulations were performed for a modified silicon dioxide surface with positively charged groups at neutral pH. The dosing of a surface with unattached oligonucleotide was simulated. The oligonucleotide was found to associate with the surface in salt water in a way that some of the bases remained stacked, and most of the bases near the surface on average pointed preferentially toward the solution, away from the surface. Use of an analytic solution to the linear Poisson–Boltzmann (PB) theory of the electric double layer interaction between DNA and a hard surface predicts tight binding in this system. The simulation thus gives a mechanism for specificity and the theory a mechanism for affinity. The geometry is such that only non-helical base pairs would be accommodated with an irregular backbone.

Keywords:

• Poisson–Boltzmann theory
• Thermodynamics
• Oligonucleotide
• Non-Watson–Crick motif

Acknowledgements

A.V. thanks Lev N. Bulaevski for discussions. B.M.P. thanks Prof. R. Georgiadis and Dr R. Mitra for discussions. This work was partially supported by grants from NIH, Texas Coordinating Board and the Robert A. Welch Foundation to B.M.P. and grants from NIH and University of Arizona to M.E.H. B.M.P. and K.Y.W. acknowledge the National Cancer Institute for allocation of computing time and staff support at the Advanced Biomedical Computing Center of the Frederick Cancer Research and Development Center, and also NPACI for computing time and support at the San Diego Supercomputing Center. We also thank the Molecular Science Computing Facility (MSCF) in the William R. Wiley Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the U.S. Department of Energy's Office of Biological and Environmental Research and located at the Pacific Northwest National Laboratory. Pacific Northwest is operated for the Department of Energy by Battelle. B.M.P. and K.Y.W. also thank Accelrys for providing visualization software through the Institute for Molecular Design.