PT  - JOURNAL ARTICLE
AU  - Tam T. M. Phan
AU  - Tien M. Phan
AU  - Jeremy D. Schmit
TI  - Beneficial and Detrimental Effects of Nonspecific Binding During DNA Hybridization
AID  - 10.1101/2022.03.31.486645
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.31.486645
4099  - http://biorxiv.org/content/early/2022/04/01/2022.03.31.486645.short
4100  - http://biorxiv.org/content/early/2022/04/01/2022.03.31.486645.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.