DNA origami and the complexity of Eulerian circuits with turning costs

Abstract: Building a structure using self-assembly of DNA molecules by origami folding requires finding a route for the scaffolding strand through the desired structure. When the target structure is a 1-complex (or the geometric realization of a graph), an optimal route corresponds to an Eulerian circuit through the graph with minimum turning cost. By showing that it leads to a solution to the 3-SAT problem, we prove that the general problem of finding an optimal route for a scaffolding strand for such structures is NP-hard. We then show that the problem may readily be transformed into a Traveling Salesman Problem (TSP), so that machinery that has been developed for the TSP may be applied to find optimal routes for the scaffolding strand in a DNA origami self-assembly process. We give results for a few special cases, showing for example that the problem remains intractable for graphs with maximum degree 8, but is polynomial time for 4-regular plane graphs if the circuit is restricted to following faces. We conclude with some implications of these results for related problems, such as biomolecular computing and mill routing problems.