Harnessing Hypergraphs in Geometric Deep Learning for 3D RNA Inverse Folding

TL;DR

This paper introduces HyperRNA, a hypergraph-based generative model for RNA inverse folding that effectively captures complex structural dependencies, outperforming existing methods in designing RNA sequences for desired structures.

Contribution

The paper presents HyperRNA, a novel hypergraph-augmented encoder-decoder framework for RNA inverse folding, leveraging higher-order dependencies for improved RNA design accuracy.

Findings

HyperRNA outperforms existing RNA design methods.

HyperRNA effectively captures higher-order dependencies in RNA structures.

Experimental results demonstrate the potential of hypergraphs in RNA engineering.

Abstract

The RNA inverse folding problem, a key challenge in RNA design, involves identifying nucleotide sequences that can fold into desired secondary structures, which are critical for ensuring molecular stability and function. The inherent complexity of this task stems from the intricate relationship between sequence and structure, making it particularly challenging. In this paper, we propose a framework, named HyperRNA, a generative model with an encoder-decoder architecture that leverages hypergraphs to design RNA sequences. Specifically, our HyperRNA model consists of three main components: preprocessing, encoding and decoding. In the preprocessing stage, graph structures are constructed by extracting the atom coordinates of RNA backbone based on 3-bead coarse-grained representation. The encoding stage processes these graphs, capturing higher order dependencies and complex biomolecular interactions using an attention embedding module and a hypergraph-based encoder. Finally, the decoding stage generates the RNA sequence in an autoregressive manner. We conducted quantitative and qualitative experiments on the PDBBind and RNAsolo datasets to evaluate the inverse folding task for RNA sequence generation and RNA-protein complex sequence generation. The experimental results demonstrate that HyperRNA not only outperforms existing RNA design methods but also highlights the potential of leveraging hypergraphs in RNA engineering.