arXiv AI

La-Ribo: RNA Co-Design via Geometry-Latent Flow Matching

La‑Ribo is a generative framework that jointly designs RNA nucleotide sequences and their three‑dimensional structures using geometry‑latent flow matching. It preserves a sparse phosphate‑sugar‑base scaffold while encoding nucleotide identity and local conformation in residue‑wise latent variables, which a shared flow network generates before an RNA‑specific decoder reconstructs all heavy atoms. The authors also built a large, quality‑controlled corpus of 168,561 RNA structures—combining experimental data with predictions from three folding models—to expand supervision, and demonstrate that La‑Ribo outperforms baselines in designability and co‑designability across sampling budgets and refolding models, while also enabling scaffold‑conditioned inverse folding without extra training.

arXiv AI
3d ago

GOLD: Geometric Optimized Latent Diffusion for Structure-Aware RNA Inverse Folding

The paper introduces GOLD, a Geometric Optimized Latent Diffusion framework that jointly models RNA sequences and their side‑chain geometries in a unified latent space using a novel GeoVAE. By co‑diffusing sequence and structure and employing a gradient‑guided sampling step that enforces physical constraints, GOLD achieves superior performance in sequence recovery, secondary structure validity, and 3D foldability compared to existing inverse‑folding methods.

By Qi Si, Xuyang Liu, Penglei Wang, Shuo Su, Limei Han, Mengzhu Li, Xin Guo, Yuan Qi, Yuan Cheng
arXiv AI
Oct 2

CODesign: Consistency from Data to Trajectory in All-Atom Protein Binder Co-Design

CODesign is a co-design framework that jointly generates protein sequences and structures to improve consistency between them. It introduces a large consistency‑distilled dataset of about 105,000 dimers and employs a multimodal joint flow model with a consistency‑aware resampling strategy to iteratively refine sequences and side chains. The approach achieves state‑of‑the‑art in silico success rates for protein‑ and ligand‑target binder design, with ablation studies showing a 70.9% performance boost from the distilled dataset and further gains from the resampling mechanism.

By Yuanle Mo, Bo Qiang, Haitao Lin, Qinghan Wang, Gang Du, Odin Zhang, Pheng Ann Heng
arXiv Machine Learning
Oct 5

RNADyn: A Benchmark for Generating and Understanding RNA Dynamics

RNADynBench is a new standardized benchmark for RNA molecular dynamics, comprising 2,585 high‑quality 100‑nanosecond all‑atom trajectories with carefully controlled data splits. RNADynNet is a unified model that simultaneously generates RNA trajectories and extracts dynamics fingerprints from a single conformer, leveraging coordinate denoising, alignment, and physical grounding. The model achieves strong agreement with MD data, achieving RMSF correlations of 0.875 and 0.766 on test sets, including a high‑flexibility challenge set.

By Yiming Huang, Lennart Bastian, Hanqun Cao, Luis Vollmers, Tolga Birdal
arXiv AI
Aug 19

Leveraging generative hallucination and biophysics-informed modeling for unified biomolecular sequence-structure co-design

The paper introduces MCTH (Monte Carlo Tree Hallucination), an inference-only framework that performs all‑atom biomolecular sequence‑structure co‑design by treating pretrained folding and inverse‑folding models as black‑box operators. MCTH uses Monte Carlo Tree Search to allocate a fixed inference budget across competing design trajectories, incorporating model confidence, uncertainty, and cross‑expert consensus. Experiments across protein‑RNA, protein‑DNA, protein‑protein, and protein‑ligand design show that adaptive search outperforms simpler sampling strategies, and evaluations with AlphaFold3 and Chai‑1 demonstrate transferability beyond the search‑time oracle.

By Xuefeng Liu, Mingxuan Cao, Xiao Luo, Songhao Jiang, Tobin Sosnick, Jinbo Xu, Louis Maher, Rick Stevens
arXiv Machine Learning
Sep 11

Sequence-Informed Geometric Evaluation of RNA 3D Structures

The paper introduces SIRGE, a sequence-informed geometric evaluator for RNA 3D structures that integrates nucleotide embeddings from a pretrained RNA language model into structural representations. SIRGE demonstrates superior performance over existing evaluators in Kendall–τ alignment, Top‑1 selection, and Top‑3 ranking. Controlled experiments reveal that sequence conditioning corrects errors of a purely geometric model and enhances target‑level ranking, suggesting that pretrained sequence representations provide complementary ranking information to geometric reasoning.

By Andrea Zerio, Yighua Yao, Alessandro Micheli, Roland G. Huber, Mile Sikic, Samir Bhatt, Andres R. Masegosa, Yuangang Pan
arXiv AI
Sep 2

SymFold: Synergizing Evolutionary and Structural Priors for Accurate Protein Inverse Folding

SymFold introduces a symmetric dual‑path architecture that combines protein language models (PLMs) and multimodal protein language models (MPLMs) to iteratively guide protein sequence generation for inverse folding. By leveraging pretrained sequence evolution knowledge from PLMs and structural knowledge from MPLMs, the method improves upon the traditional serial pipeline where structure encoders produce coarse sequences refined by PLMs. Experiments on standard inverse‑folding benchmarks show state‑of‑the‑art performance, and ablation studies confirm the effectiveness of the symmetric design.

By Handong Wang, Jiaxin Qi, Baisheng Lai, Jianqiang Huang
arXiv Machine Learning
Oct 12

Scaling RNA Foundation Models through Iterative Refinement

Eco‑RNA is an 80‑million‑parameter RNA foundation model that introduces adjustable inference depth via learned iterative refinement. The shared, input‑conditioned Transformer core repeatedly refines sequence representations, with the number of iterations chosen after training to control effective depth. On the RNAGym fitness benchmark, increasing iterations from one to four improves Spearman correlation from 0.242 to 0.286, and at four iterations Eco‑RNA outperforms the 40‑billion‑parameter Evo 2 model across all aggregate fitness metrics, while also excelling in non‑coding RNA classification, secondary‑structure prediction, and chemical probing profile prediction.

By Pengan Chen, Liang Hong, Xinyuan Liu, Han Huang, Ziqian Lin, Jiayang Chen, Yimin Fan, Jiyue Jiang, Yu Li