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bioRxiv · 10.1101/2022.03.31.486645

Beneficial and Detrimental Effects of Nonspecific Binding During DNA Hybridization

Phan, T. T. M.·Phan, T. M.·Schmit, J. D.
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Abstract

DNA strands have to sample numerous states to find the alignment that maximizes Watson-Crick-Franklin base pairing. This process depends strongly on sequence, which affects the stability of the native duplex as well as the prevalence of non-native inter- and intra-molecular helices. We present a theory which describes DNA hybridization as a three stage process: diffusion, registry search, and zipping. We find that non-specific binding affects each of these stages in different ways. Mis-registered intermolecular binding in the registry search stage helps DNA strands sample different alignments and accelerates the hybridization rate. Non-native intramolecular structure affects all three stages by rendering portions of the molecule inert to intermolecular association, limiting mis-registered alignments to be sampled, and impeding the zipping process. Once inregister base-pairs are formed, the stability of the native structure is important to hold the molecules together long enough for non-native contacts to break.

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Phan, T. T. M., Phan, T. M., Schmit, J. D.. 2022-04-01. Beneficial and Detrimental Effects of Nonspecific Binding During DNA Hybridization. https://doi.org/10.1101/2022.03.31.486645

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