Simulation-guided DNA probe design for consistently ultraspecific hybridization.

ABSTRACT: Hybridization of complementary sequences is one of the central tenets of nucleic acid chemistry; however, the unintended binding of closely related sequences limits the accuracy of hybridization-based approaches to analysing nucleic acids. Thermodynamics-guided probe design and empirical optimization of the reaction conditions have been used to enable the discrimination of single-nucleotide variants, but typically these approaches provide only an approximately 25-fold difference in binding affinity. Here we show that simulations of the binding kinetics are both necessary and sufficient to design nucleic acid probe systems with consistently high specificity as they enable the discovery of an optimal combination of thermodynamic parameters. Simulation-guided probe systems designed against 44

SUBMITTER: Wang JS 

PROVIDER: S-EPMC4479422 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature