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Designing protein mutants of both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants of improved stability and activity…

Protein language models such as ESM-2 learn rich residue representations that achieve strong performance on protein function prediction, but their features remain difficult to interpret as structural $\&$ evolutionary signals are encoded in…

Machine Learning · Computer Science 2026-05-13 Siddhant Dutta , Edward Tan Beng Wai , Soumick Sarker , Pasan Gunawardane , Jagath C. Rajapakse

Protein post-translational modification (PTM) site prediction is a fundamental task in bioinformatics. Several computational methods have been developed to predict PTM sites. However, existing methods ignore the structure information and…

Quantitative Methods · Quantitative Biology 2024-01-19 Zhengyi Li , Menglu Li , Lida Zhu , Wen Zhang

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…

Machine Learning · Computer Science 2023-10-05 Zhenqiao Song , Yunlong Zhao , Yufei Song , Wenxian Shi , Yang Yang , Lei Li

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor…

Biomolecules · Quantitative Biology 2023-11-29 Shikun Feng , Minghao Li , Yinjun Jia , Weiying Ma , Yanyan Lan

Determining the structure of a protein has been a decades-long open question. A protein's three-dimensional structure often poses nontrivial computation costs, when classical simulation algorithms are utilized. Advances in the transformer…

Machine Learning · Computer Science 2023-10-09 Chen Dun , Qiutai Pan , Shikai Jin , Ria Stevens , Mitchell D. Miller , George N. Phillips, , Anastasios Kyrillidis

Protein-specific large language models (Protein LLMs) are revolutionizing protein science by enabling more efficient protein structure prediction, function annotation, and design. While existing surveys focus on specific aspects or…

Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or…

Proteins play a central role in biology from immune recognition to brain activity. While major advances in machine learning have improved our ability to predict protein structure from sequence, determining protein function from structure…

Understanding the spatial architecture of the tumor microenvironment (TME) is critical to advance precision oncology. We present ProteinPNet, a novel framework based on prototypical part networks that discovers TME motifs from spatial…

Machine Learning · Computer Science 2025-12-03 Louis McConnell , Jieran Sun , Theo Maffei , Raphael Gottardo , Marianna Rapsomaniki

As proteins with similar structures often have similar functions, analysis of protein structures can help predict protein functions and is thus important. We consider the problem of protein structure classification, which computationally…

Machine Learning · Statistics 2019-10-08 Hongyu Guo , Khalique Newaz , Scott Emrich , Tijana Milenkovic , Jun Li

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Identifying DNA- (DBPs) and RNA-binding proteins (RBPs) is crucial for the understanding of cell function, molecular interactions as well as regulatory functions. Owing to their high similarity, most of the existing approaches face…

Quantitative Methods · Quantitative Biology 2025-10-22 Nimisha Ghosh , Dheeran Sankaran , Rahul Balakrishnan Adhi , Sharath S , Amrut Anand

Protein-protein interaction (PPI) prediction is an instrumental means in elucidating the mechanisms underlying cellular operations, holding significant practical implications for the realms of pharmaceutical development and clinical…

Machine Learning · Computer Science 2025-03-07 Jiang Li , Xiaoping Wang

Predicting protein secondary structures such as alpha helices, beta sheets, and coils from amino acid sequences is essential for understanding protein function. This work presents a transformer-based model that applies attention mechanisms…

Artificial Intelligence · Computer Science 2025-12-10 Manzi Kevin Maxime

The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

Protein secondary structure prediction is an important problem in bioinformatics. Inspired by the recent successes of deep neural networks, in this paper, we propose an end-to-end deep network that predicts protein secondary structures from…

Biomolecules · Quantitative Biology 2016-04-27 Zhen Li , Yizhou Yu

The analysis of the three-dimensional structure of proteins is an important topic in molecular biochemistry. Structure plays a critical role in defining the function of proteins and is more strongly conserved than amino acid sequence over…

Applications · Statistics 2015-01-19 Abel Rodriguez , Scott C. Schmidler

Signaling proteins are an important topic in drug development due to the increased importance of finding fast, accurate and cheap methods to evaluate new molecular targets involved in specific diseases. The complexity of the protein…

Quantitative Methods · Quantitative Biology 2019-04-11 Carlos Fernandez-Lozano , Ruben F. Cuinas , Jose A. Seoane , Enrique Fernandez-Blanco , Julian Dorado , Cristian R. Munteanu

Current language models tailored for code tasks often adopt the pre-training-then-fine-tuning paradigm from natural language processing, modeling source code as plain text. This approach, however, overlooks the unambiguous structures…

Computation and Language · Computer Science 2024-01-22 Mayank Agarwal , Yikang Shen , Bailin Wang , Yoon Kim , Jie Chen