Structure sampling for computational estimation of localized DNA interaction rates

Molecular circuits implemented using molecular components tethered to a DNA tile nanostructure have certain advantages over solution-phase circuits. Tethering components in close proximity increases the speed of reactions by reducing diffusion and improves scalability by enabling reuse of identical DNA sequences at different locations in the circuit. These systems show great potential for practical applications including delivery of diagnostic and therapeutic molecular circuits to cells. When modeling such systems, molecular geometry plays an important role in determining whether the two species interact and at what rate. In this paper, we present an automated method for estimating reaction rates in tethered molecular circuits that takes the geometry of the tethered species into account. We probabilistically generate samples of structure distributions based on simple biophysical models and use these to estimate important parameters for kinetic models. This work provides a basis for subsequent enhanced modeling and design tools for localized molecular circuits.