What are the Dynamics of DNA Nanocages? From Design to Applications in Drug Delivery

Abstract

Designer drugs, which can be both specific and customizable, are an area of ongoing research. However, the development of novel drugs is prohibitively expensive. A way to avoid this issue is to build a highly controlled and modifiable scaffold that is non toxic to the body. DNA Nanocages, which use the principles of Watson-Crick base pairing to form regular prismatic shapes is such a scaffold. They achieve such a feat by only using part of the DNA material to build the shape; leaving segments of single stranded DNA to which a complementary strand can bind. This complementary strand opens up the utility of the scaffold by either itself being the delivery component, or by attaching to such a component. In order to optimally use the DNA Nanocages as a scaffold we must understand their dynamics. The only way to get a truly atomistic understanding is to use computational simulations. To achieve this we designed a new program, DNA-BACon, to automate the construction of the DNA Nanocages. This allowed us to test a variety of shapes using both molecular and metadynamic simulations. Thus gaining insight into their different thermodynamic properties. Specifically the various transition states; their rate and energy barriers. Consequently informing us of how rigid or flexible our scaffold is, the potential conformations it can take, and thus understanding of appropriate components and how to add them. Ultimately giving invaluable insight into the development of a new type of medical materials from which a cornucopia of potential therapies can be created.