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In cancer therapeutics, protein-metal binding mechanisms critically govern the pharmacokinetics and targeting efficacy of drugs, thereby fundamentally shaping the rational design of anticancer metallodrugs. While conventional laboratory…

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

Antibody-based therapeutics-including antibody-drug conjugates (ADCs), bispecific antibodies, and novel formats-are reshaping oncology, yet key determinants of efficacy, safety, and manufacturability frequently emerge after conjugation and…

Soft Condensed Matter · Physics 2026-05-18 Alberto Ocana , Jorge R. Espinosa

Recent advancements in immune sequencing and experimental techniques are generating extensive T cell receptor (TCR) repertoire data, enabling the development of models to predict TCR binding specificity. Despite the computational challenges…

Quantitative Methods · Quantitative Biology 2024-07-24 Anna Weber , Aurélien Pélissier , María Rodríguez Martínez

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially…

Quantitative Methods · Quantitative Biology 2022-10-18 Mingyang Hu , Fajie Yuan , Kevin K. Yang , Fusong Ju , Jin Su , Hui Wang , Fei Yang , Qiuyang Ding

With the growing prominence of antibody-based therapeutics, antibody engineering has gained increasing attention as a critical area of research and development. Recent progress in transformer-based protein large language models (LLMs) has…

Machine Learning · Computer Science 2025-06-17 Eunna Huh , Hyeonsu Lee , Hyunjin Shin

The anti-cancer immune response relies on the bindings between T-cell receptors (TCRs) and antigens, which elicits adaptive immunity to eliminate tumor cells. This ability of the immune system to respond to novel various neoantigens arises…

Quantitative Methods · Quantitative Biology 2025-11-11 Xing Fang , Chenpeng Yu , Shiye Tian , Hui Liu

Predicting the binding free energy between antibodies and antigens is a key challenge in structure-aware biomolecular modeling, with direct implications for antibody design. Most existing methods either rely solely on sequence embeddings or…

Biomolecules · Quantitative Biology 2025-08-28 Ciyuan Yu , Hongzong Li , Jiahao Ma , Shiqin Tang , Ye-Fan Hu , Jian-Dong Huang

Large language models applied to vast biological datasets have the potential to transform biology by uncovering disease mechanisms and accelerating drug development. However, current models are often siloed, trained separately on…

In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic…

Quantitative Methods · Quantitative Biology 2023-05-08 Yining Wang , Xumeng Gong , Shaochuan Li , Bing Yang , YiWu Sun , Chuan Shi , Yangang Wang , Cheng Yang , Hui Li , Le Song

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

Protein language models (PLMs) have revolutionised computational biology through their ability to generate powerful sequence representations for diverse prediction tasks. However, their black-box nature limits biological interpretation and…

Biomolecules · Quantitative Biology 2025-04-11 Jan van Eck , Dea Gogishvili , Wilson Silva , Sanne Abeln

A plethora of protein language models have been released in recent years. Yet comparatively little work has addressed how to best sample from them to optimize desired biological properties. We fill this gap by proposing a flexible,…

Machine Learning · Computer Science 2026-05-08 Calvin McCarter , Nick Bhattacharya , Sebastian W. Ober , Hunter Elliott

The Complementarity Determining Region (CDR) structure prediction of loops in antibody engineering has gained a lot of attraction by researchers. When designing antibodies, a main challenge is to predict the CDR structure of the H3 loop.…

Machine Learning · Computer Science 2023-06-23 Eleni Giovanoudi , Dimitrios Rafailidis

Antibodies comprise the most versatile class of binding molecules, with numerous applications in biomedicine. Computational design of antibodies involves generating novel and diverse sequences, while maintaining structural consistency.…

Biomolecules · Quantitative Biology 2023-06-21 Igor Melnyk , Vijil Chenthamarakshan , Pin-Yu Chen , Payel Das , Amit Dhurandhar , Inkit Padhi , Devleena Das

Predicting molecular properties is a critical component of drug discovery. Recent advances in deep learning, particularly Graph Neural Networks (GNNs), have enabled end-to-end learning from molecular structures, reducing reliance on manual…

Computation and Language · Computer Science 2025-09-26 Peng Zhou , Lai Hou Tim , Zhixiang Cheng , Kun Xie , Chaoyi Li , Wei Liu , Xiangxiang Zeng

Effective protein representation learning is crucial for predicting protein functions. Traditional methods often pretrain protein language models on large, unlabeled amino acid sequences, followed by finetuning on labeled data. While…

Biomolecules · Quantitative Biology 2024-09-05 Jiangbin Zheng , Stan Z. Li

Protein engineering is an emerging field in biotechnology that has the potential to revolutionize various areas, such as antibody design, drug discovery, food security, ecology, and more. However, the mutational space involved is too vast…

Biomolecules · Quantitative Biology 2023-07-28 Yuchi Qiu , Guo-Wei Wei

Protein language models (PLMs) have emerged as powerful tools to detect complex patterns of protein sequences. However, the capability of PLMs to fully capture information on protein sequences might be limited by focusing on single…

Machine Learning · Computer Science 2025-05-27 Hazem Alsamkary , Mohamed Elshaffei , Mohamed Elkerdawy , Ahmed Elnaggar

Artificial Intelligence models have demonstrated significant success in diagnosing skin diseases, including cancer, showing the potential to assist clinicians in their analysis. However, the interpretability of model predictions must be…

Computer Vision and Pattern Recognition · Computer Science 2025-08-29 Max Torop , Masih Eskandar , Nicholas Kurtansky , Jinyang Liu , Jochen Weber , Octavia Camps , Veronica Rotemberg , Jennifer Dy , Kivanc Kose