The prediction of RNA-small molecule binding sites in RNA structures based on geometric deep learning.

Biological interactions between RNA and small-molecule ligands play a crucial role in determining the specific functions of RNA, such as catalysis and folding, and are essential for guiding drug design in the medical field. Accurately predicting the binding sites of ligands within RNA structures is therefore of significant importance. To address this challenge, we introduced a computational approach named RLBSIF (RNA-Ligand Binding Surface Interaction Fingerprints) based on geometric deep learning. This model utilizes surface geometric features, including shape index and distance-dependent curvature, combined with chemical features represented by atomic charge, to comprehensively characterize RNA-ligand interactions through MaSIF-based surface interaction fingerprints. Additionally, we employ the ResNet18 network to analyze these fingerprints for identifying ligand binding pockets. Trained on 440 binding pockets, RLBSIF achieves an overall pocket-level classification accuracy of 90 %. Through a full-space enumeration method, it can predict binding sites at nucleotide resolution. In two independent tests, RLBSIF outperformed competing models, demonstrating its efficacy in accurately identifying binding sites within complex molecular structures. This method shows promise for drug design and biological product development, providing valuable insights into RNA-ligand interactions and facilitating the design of novel therapeutic interventions. For access to the related source code, please visit RLBSIF on GitHub (https://github.com/ZUSTSTTLAB/RLBSIF).