arXiv AI By Lisheng Zhang, Qingsong Li, Zinan Xie, Yanting Yang, Qikui Yang, Peng Lu, Zhican Fu, Wentao Cui, Runtong Hou, Zhengwei Xie

Predicting protein structures at any folding stage from sequence

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arXiv AI
Oct 28

Structure, Not Sequence: Tracking and Validating Folding Mechanisms in ESMFold's Trunk with Sparse Autoencoders

The paper investigates how ESMFold’s folding trunk transforms amino‑acid sequences into 3D protein structures by using sparse autoencoders (SAEs) to uncover interpretable features. It first analyzes representation distributions across modules and recycles to identify distinct spatial computations, then shows that single representations carry inherited semantics while pair representations compute pairwise geometry. Finally, the authors use a reasoning language model and gradient‑based attribution to trace concept composition across blocks, verifying alignment with known biochemistry and demonstrating that the trained sparse dictionaries can predict the model’s fold quality, thereby turning the black‑box trunk into an interpretable, scientifically verifiable circuit.

By Bohan Liu, Xiaohan Fan, Wenqian Ye, Aidong Zhang
arXiv Machine Learning
Oct 2

ProtScape: A molecular structure and energy-aware representation for protein conformation generation

arXiv:2410.20317v2 Announce Type: replace Abstract: Molecular dynamics (MD) simulations are a principled but computationally expensive approach for studying protein conformational variability, making...

By Siddharth Viswanath, Xingzhi Sun, Lucas Lee, Danqi Liao, Hiren Madhu, David R. Johnson, Jo\~ao Felipe Rocha, Egbert Castro, Jackson D. Grady, Michael Perlmutter, Dhananjay Bhaskar, Smita Krishnaswamy
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