Deep Learning Framework for RNA Inverse Folding with Geometric Structure Potentials

Abstract

RNA's diverse biological functions stem from its structural versatility, yet accurately predicting and designing RNA sequences given a 3D conformation (inverse folding) remains a challenge. Here, I introduce a deep learning framework that integrates Geometric Vector Perceptron (GVP) layers with a Transformer architecture to enable end-to-end RNA design. I construct a dataset consisting of experimentally solved RNA 3D structures, filtered and deduplicated from the BGSU RNA list, and evaluate performance using both sequence recovery rate and TM-score to assess sequence and structural fidelity, respectively. On standard benchmarks and RNA-Puzzles, my model achieves state-of-the-art performance, with recovery and TM-scores of 0.481 and 0.332, surpassing existing methods across diverse RNA families and length scales. Masked family-level validation using Rfam annotations confirms strong generalization beyond seen families. Furthermore, inverse-folded sequences, when refolded using AlphaFold3, closely resemble native structures, highlighting the critical role of geometric features captured by GVP layers in enhancing Transformer-based RNA design.