Advancing RNA 3D structure prediction: Exploring hierarchical and hybrid approaches in CASP15

In CASP15, we used an integrated hierarchical and hybrid approach to predict RNA structures. The approach involves three steps. First, with the use of physics-based methods, Vfold2D-MC and VfoldMCPX, we predict the 2D structures from the sequence. Second, we employ template-based methods, Vfold3D and VfoldLA, to build 3D scaffolds for the predicted 2D structures. Third, using the 3D scaffolds as initial structures and the predicted 2D structures as constraints, we predict the 3D structure from coarse-grained molecular dynamics simulations, IsRNA and RNAJP. Our approach was evaluated on 12 RNA targets in CASP15 and ranked second among all the 34 participating teams. The result demonstrated the reliability of our method in predicting RNA 2D structures with high accuracy and RNA 3D structures with moderate accuracy. Further improvements in RNA structure prediction for the next round of CASP may come from the incorporation of the physics-based method with machine learning techniques.