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How a Ligand WorksThe ligand travels through the watery fluids of an organism, within the blood, tissues, or within a cell itself. The ligand travels at random, but once the concentration is high enough, a ligand will eventually reach a protein. Proteins receiving ligands can be receptors, channels, and can even be the start of a complex series of intertwined proteins. When the ligand binds to the protein, it undergoes a conformational change. This means that while no chemical bonds have been formed or broken, the physical action of the ligand fitting into the protein changes the overall shape of the entire structure. This can trigger many actions. In most cases, the movement of the protein itself activates another chemical pathway, or triggers the release of another messenger ligand, to carry the message to other receptorsDNA FREQUENCY CRYSTALSDNA has been used as a robust material for the building of a variety of nanoscale structures and devices owing to its unique properties. Structural DNA nanotechnology has reported a wide range of applications including computing, photonics, synthetic biology, biosensing, bioimaging, and therapeutic delivery, among others. Nevertheless, the foundational goal of structural DNA nanotechnology is exploiting DNA molecules to build three-dimensional crystals as periodic molecular scaffolds to precisely align, obtain, or collect desired guest molecules. Over the past 30 years, a series of 3D DNA crystals have been rationally designed and developed. This review aims to showcase various 3D DNA crystals, their design, optimization, applications, and the crystallization conditions utilized. Additionally, the history of nucleic acid crystallography and potential future directions for 3D DNA crystals in the era of nanotechnology are discussed.https://onlinelibrary.wiley.com › doi › 10.1002 › advs.20230202 DNA FREQUENCY CRYSTALSDNA has been used as a robust material for the building of a variety of nanoscale structures and devices owing to its unique properties. Structural DNA nanotechnology has reported a wide range of applications including computing, photonics, synthetic biology, biosensing, bioimaging, and therapeutic delivery, among others. Nevertheless, the foundational goal of structural DNA nanotechnology is exploiting DNA molecules to build three-dimensional crystals as periodic molecular scaffolds to precisely align, obtain, or collect desired guest molecules. Over the past 30 years, a series of 3D DNA crystals have been rationally designed and developed. This review aims to showcase various 3D DNA crystals, their design, optimization, applications, and the crystallization conditions utilized. Additionally, the history of nucleic acid crystallography and potential future directions for 3D DNA crystals in the era of nanotechnology are discussed.https://onlinelibrary.wiley.com › doi › 10.1002 › advs.20230202