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Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the…

Large "instruction-tuned" language models (i.e., finetuned to respond to instructions) have demonstrated a remarkable ability to generalize zero-shot to new tasks. Nevertheless, they depend heavily on human-written instruction data that is…

Computation and Language · Computer Science 2023-05-29 Yizhong Wang , Yeganeh Kordi , Swaroop Mishra , Alisa Liu , Noah A. Smith , Daniel Khashabi , Hannaneh Hajishirzi

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Large language models (LLMs) have demonstrated significant success in natural language processing (NLP) tasks and have shown promising results in other domains such as protein sequence generation. However, there remain salient differences…

Biomolecules · Quantitative Biology 2024-11-12 Aayush Shah , Shankar Jayaratnam

Protein design aims to compose amino-acid sequences that fold into stable three-dimensional structures while satisfying targeted functional properties. The field is increasingly shifting toward vibe protein design, where a single model is…

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Large Language Models (LLMs) demonstrate strong performance in real-world applications, yet existing open-source instruction datasets often concentrate on narrow domains, such as mathematics or coding, limiting generalization and widening…

Computation and Language · Computer Science 2025-06-16 Jijie Li , Li Du , Hanyu Zhao , Bo-wen Zhang , Liangdong Wang , Boyan Gao , Guang Liu , Yonghua Lin

We propose ProtLLM, a versatile cross-modal large language model (LLM) for both protein-centric and protein-language tasks. ProtLLM features a unique dynamic protein mounting mechanism, enabling it to handle complex inputs where the natural…

Biomolecules · Quantitative Biology 2024-03-14 Le Zhuo , Zewen Chi , Minghao Xu , Heyan Huang , Heqi Zheng , Conghui He , Xian-Ling Mao , Wentao Zhang

Designing protein sequences of both high fitness and novelty is a challenging task in data-efficient protein engineering. Exploration beyond wild-type neighborhoods often leads to biologically implausible sequences or relies on surrogate…

Machine Learning · Computer Science 2025-10-28 Michal Kmicikiewicz , Vincent Fortuin , Ewa Szczurek

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…

Understanding biological processes, drug development, and biotechnological advancements requires a detailed analysis of protein structures and functions, a task that is inherently complex and time-consuming in traditional protein research.…

Artificial Intelligence · Computer Science 2025-04-21 Yijia Xiao , Edward Sun , Yiqiao Jin , Qifan Wang , Wei Wang

Less than 1% of protein sequences are structurally and functionally annotated. Natural Language Processing (NLP) community has recently embraced self-supervised learning as a powerful approach to learn representations from unlabeled text,…

Biomolecules · Quantitative Biology 2020-12-08 Modestas Filipavicius , Matteo Manica , Joris Cadow , Maria Rodriguez Martinez

Computational protein design is experiencing a transformation driven by AI/ML. However, the range of potential protein sequences and structures is astronomically vast, even for moderately sized proteins. Hence, achieving convergence between…

Distributed, Parallel, and Cluster Computing · Computer Science 2025-10-09 Aymen Alsaadi , Jonathan Ash , Mikhail Titov , Matteo Turilli , Andre Merzky , Shantenu Jha , Sagar Khare

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent…

Computation and Language · Computer Science 2025-05-30 Wei Wu , Chao Wang , Liyi Chen , Mingze Yin , Yiheng Zhu , Kun Fu , Jieping Ye , Hui Xiong , Zheng Wang

Designing de novo proteins beyond those found in nature holds significant promise for advancements in both scientific and engineering applications. Current methodologies for protein design often rely on AI-based models, such as surrogate…

Soft Condensed Matter · Physics 2024-02-08 A. Ghafarollahi , M. J. Buehler

De novo ligand design is a fundamental task that seeks to generate protein or molecule candidates that can effectively dock with protein receptors and achieve strong binding affinity entirely from scratch. It holds paramount significance…

Machine Learning · Computer Science 2025-10-13 Zekai Chen , Xunkai Li , Sirui Zhang , Henan Sun , Jia Li , Zhenjun Li , Bing Zhou , Rong-Hua Li , Guoren Wang

Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express…

Computational Engineering, Finance, and Science · Computer Science 2025-10-27 Xiao Fei , Michail Chatzianastasis , Sarah Almeida Carneiro , Hadi Abdine , Lawrence P. Petalidis , Michalis Vazirgiannis

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering…

Biomolecules · Quantitative Biology 2023-09-01 Hongtai Jing , Zhengtao Gao , Sheng Xu , Tao Shen , Zhangzhi Peng , Shwai He , Tao You , Shuang Ye , Wei Lin , Siqi Sun

Binding affinity optimization is crucial in early-stage drug discovery. While numerous machine learning methods exist for predicting ligand potency, their comparative efficacy remains unclear. This study evaluates the performance of…

Biomolecules · Quantitative Biology 2024-07-30 Nikolai Schapin , Carles Navarro , Albert Bou , Gianni De Fabritiis

The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar