Engineering multistate DNA molecules: a tunable thermal band‐pass filter

Abstract

Engineering of biopolymer ‘partner folds’ that exist in competitive equilibrium with the native state to produce exotic behaviours remains a relatively unexplored area of molecular engineering. Previously, a temperature-sensitive DNA nanodevice that operates by harnessing such a partner fold to implement a thermal band-pass filter was proposed, modelled, and experimentally validated. Due to its peculiar hill-shaped efficiency profile, which differs markedly from the sigmoidal melting curves of simple DNA hairpins, this device could be used to implement temperature-specific control of other molecular machines, and thus represents a promising biotechnological advance. However, no effort was made to examine the detailed dependencies of the peak temperature T †, width ΔT 50, and maximum efficiency e max on the stabilities of device components. In this work, closed-form expressions for T † and ln e max are derived and validated. The functional behaviours of these expressions are then examined and harnessed to construct an efficient algorithm for producing designs with target T † and ΔT 50 values and optimised e max, thereby establishing the feasibility of algorithmic device design. Method effectiveness is validated via production of a target filter, with detailed simulations of device behaviour. Finally, a discussion is presented regarding model effectiveness, extension, and scope.