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Engineering molecular systems that exhibit complex behavior requires the design of kinetic barriers. For example, an effective catalytic pathway must have a large barrier when the catalyst is absent. While programming such energy barriers…

Emerging Technologies · Computer Science 2020-01-28 Keenan Breik , Cameron Chalk , David Doty , David Haley , David Soloveichik

The affinity and specificity of protein-molecule binding directly impact functional outcomes, uncovering the mechanisms underlying biological regulation and signal transduction. Most deep-learning-based prediction approaches focus on…

Machine Learning · Computer Science 2025-06-03 Haitao Lin , Odin Zhang , Jia Xu , Yunfan Liu , Zheng Cheng , Lirong Wu , Yufei Huang , Zhifeng Gao , Stan Z. Li

Accurate identification of protein nucleic-acid-binding residues poses a significant challenge with important implications for various biological processes and drug design. Many typical computational methods for protein analysis rely on a…

Biomolecules · Quantitative Biology 2023-12-21 Linglin Jing , Sheng Xu , Yifan Wang , Yuzhe Zhou , Tao Shen , Zhigang Ji , Hui Fang , Zhen Li , Siqi Sun

We introduce IntFold, a controllable foundation model for general and specialized biomolecular structure prediction. Utilizing a high-performance custom attention kernel, IntFold achieves accuracy comparable to the state-of-the-art…

Biomolecules · Quantitative Biology 2025-07-08 The IntFold Team , Leon Qiao , Wayne Bai , He Yan , Gary Liu , Nova Xi , Xiang Zhang , Siqi Sun

Predicting enzyme-substrate interactions has long been a fundamental problem in biochemistry and metabolic engineering. While existing methods could leverage databases of expert-curated enzyme-substrate pairs for models to learn from known…

Artificial Intelligence · Computer Science 2026-01-12 Tengwei Song , Long Yin , Zhen Han , Zhiqiang Xu

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

The design and implementation of regulation motifs ensuring robust perfect adaptation are challenging problems in synthetic biology. Indeed, the design of high-yield robust metabolic pathways producing, for instance, drug precursors and…

Optimization and Control · Mathematics 2021-12-21 Corentin Briat , Christoph Zechner , Mustafa Khammash

As experimental efforts are costly and time consuming, computational characterization of enzyme capabilities is an attractive alternative. We present and evaluate several machine-learning models to predict which of 983 distinct enzymes, as…

Cell Behavior · Quantitative Biology 2021-01-27 Gian Marco Visani , Michael C. Hughes , Soha Hassoun

Kinetic parameters such as the turnover number ($k_{cat}$) and Michaelis constant ($K_{\mathrm{M}}$) are essential for modelling enzymatic activity but experimental data remains limited in scale and diversity. Previous methods for…

Quantitative Methods · Quantitative Biology 2025-07-22 Saleh Alwer , Ronan Fleming

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Quantitative Methods · Quantitative Biology 2023-12-04 Chuanrui Wang , Bozitao Zhong , Zuobai Zhang , Narendra Chaudhary , Sanchit Misra , Jian Tang

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…

Protein binder design is central to therapeutics, diagnostics, and synthetic biology, yet practical deployment remains challenging due to fragmented workflows, high computational costs, and complex tool integration. We present…

Biomolecules · Quantitative Biology 2025-05-29 Jie Gao , Jun Li , Jing Hu , Shanzhuo Zhang , Kunrui Zhu , Yueyang Huang , Xiaonan Zhang , Xiaomin Fang

Understanding protein solubility is essential for their functional applications. Computational methods for predicting protein solubility are crucial for reducing experimental costs and enhancing the efficiency and success rates of protein…

Quantitative Methods · Quantitative Biology 2024-07-01 Yang Tan , Jia Zheng , Liang Hong , Bingxin Zhou

Structural biology has long been dominated by the one sequence, one structure, one function paradigm, yet many critical biological processes - from enzyme catalysis to membrane transport - depend on proteins that adopt multiple…

Enzymes, with their specific catalyzed reactions, are necessary for all aspects of life, enabling diverse biological processes and adaptations. Predicting enzyme functions is essential for understanding biological pathways, guiding drug…

Machine Learning · Computer Science 2024-10-02 Chenqing Hua , Bozitao Zhong , Sitao Luan , Liang Hong , Guy Wolf , Doina Precup , Shuangjia Zheng

Recent advances in protein backbone generation have achieved promising results under structural, functional, or physical constraints. However, existing methods lack the flexibility for precise topology control, limiting navigation of the…

Artificial Intelligence · Computer Science 2025-04-22 Zhengxi Lu , Shizhuo Cheng , Yuru Jiang , Yan Zhang , Min Zhang

Newly-translated glycoproteins in the endoplasmic reticulum (ER) often undergo cycles of chaperone binding and release in order to assist in folding. Quality control is required to distinguish between proteins that have completed native…

Biological Physics · Physics 2021-06-09 Aidan I Brown , Elena F Koslover

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren

Enzyme-substrate kinetics form the basis of many biomolecular processes. The interplay between substrate binding and substrate geometry can give rise to long-range interactions between enzyme binding events. Here, we study a general model…

Biological Physics · Physics 2024-01-19 Fabrizio Olmeda , Steffen Rulands