AlphaFold 3 Modeling of DNA Nanomotifs: Is It Reliable?

Being able to accurately predict structures is highly desirable for nanoengineering with DNA and other biomolecules. The newly launched AlphaFold 3 (AF3) provides a potential platform for this purpose. In this work, we have used AF3 to model a list of commonly used DNA nanomotifs and compared the AF3 structures with the experimentally observed structures reported in literature. Some are consistent, while others are substantially different. This study suggests that while AF3 is immensely helpful, we as experimentalists should use it (as it currently stands) with caution. In addition, AF3 needs further development to incorporate the existing experimental data in the training dataset for AF3. At the current stage, a hybrid approach might be beneficial: theoretical modeling softwares calculate the detailed, 3D DNA structures based on secondary DNA structures inspired by experimental observations.