Modelling and Simulation of DNA-Based Nanomaterials

In nature, simple molecular building blocks self-assemble into complex structures to achieve outstanding functionality. For example, proteins are made up of amino acids and DNA (deoxyribonucleic acid) is made up of nucleotides. Proteins and DNA are involved in most processes in life, from genetic encoding of information to enzyme catalysis. The large sequence space and the variation of the physicochemical properties of biomolecules leads to their functional diversity. Inspired by the superior properties of such self-assembled systems, materials with unique properties can be designed. The base pair complementarity of DNA and the origami method laid the foundation for the field of DNA nanotechnology and synthesis of 2D and 3D nanostructures of desired geometry. Bioconjugate chemistry enables the modification of DNA strands with functional molecules that can be designed with optimized spacings and orientations within the DNA backbone, leading to applications in energy transfer, vaccine development, or enzyme catalysis.<br/><br/>In this work, we present the design of DNA origami for the development of functional nanostructures. Modeling and simulation have been used to better understand the molecular structure of functional DNA structures and to guide new designs. The 2D and 3D DNA structures were first generated using the ATHENA software package, followed by coarse-grained oxDNA simulations to investigate the structural integrity of the DNA nanostructures. As an example, hybrids of DNA wireframe structures decorated with fluorescent molecules have been tailored to achieve the desired spectroscopic properties. The goal was to mimic and engineer the outstanding efficiency of fluorophores in large protein complexes such as the light-harvesting antenna complex. Fully atomistic molecular dynamics (MD) simulations provided further insights. This approach enables the design of hybrid systems with functional properties for applications where molecules need to be arranged on the nanometer scale.<br/><br/><b>References</b><br/>X. Wang^#, S. Li^#, H. Jun^#, <b><u>T. John</u></b>, K. Zhang, H. Fowler, J.P.K. Doye, W. Chiu*, M. Bathe*, Planar 2D Wireframe DNA Origami, <i>Sci. Adv.</i> 8 (<b>2022</b>) eabn0039.<br/><br/>H. Jun, X. Wang, M.F. Parsons, W.P. Bricker, <b><u>T. John</u></b>, S. Li, S. Jackson, W. Chiu, M. Bathe*, Rapid prototyping of arbitrary 2D and 3D wireframe DNA origami, <i>Nucleic Acids Res.</i> 49 (<b>2021</b>) 10265–10274.