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Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the…

Quantitative Methods · Quantitative Biology 2024-08-14 Kamyar Zeinalipour , Neda Jamshidi , Monica Bianchini , Marco Maggini , Marco Gori

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

Protein analysis tasks arising in healthcare settings often require accurate reasoning under protein sequence constraints, involving tasks such as functional interpretation of disease-related variants, protein-level analysis for clinical…

Artificial Intelligence · Computer Science 2026-03-03 Congying Liu , Taihao Li , Ming Huang , Xingyuan Wei , Peipei Liu , Yiqing Shen , Yanxu Mao , Tiehan Cui

Large language models (LLMs) can face factual limitations when responding to time-sensitive queries about recent events that arise after their knowledge thresholds in the training corpus. Existing search-augmented approaches fall into two…

Information Retrieval · Computer Science 2025-06-11 Wentao Shi , Yiqing Shen

Large Language Models (LLMs) are primarily trained on high-resource natural languages, limiting their effectiveness in low-resource settings and in tasks requiring deep logical reasoning. This research introduces Rosetta-PL, a benchmark…

Computation and Language · Computer Science 2025-05-06 Shaun Baek , Shaun Esua-Mensah , Cyrus Tsui , Sejan Vigneswaralingam , Abdullah Alali , Michael Lu , Vasu Sharma , Sean O'Brien , Kevin Zhu

Existing large language models (LLMs) driven search agents typically rely on prompt engineering to decouple the user queries into search plans, limiting their effectiveness in complex scenarios requiring reasoning. Furthermore, they suffer…

Information Retrieval · Computer Science 2025-05-27 Jinzheng Li , Sibo Ju , Yanzhou Su , Hongguang Li , Yiqing Shen

Protein language models (PLMs) have demonstrated remarkable capabilities in learning relationships between protein sequences and functions. However, finetuning these large models requires substantial computational resources, often with…

Machine Learning · Computer Science 2025-12-09 Shuo Zhang , Jian K. Liu

Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML)…

Large Language Models (LLMs) have long held sway in the realms of artificial intelligence research. Numerous efficient techniques, including weight pruning, quantization, and distillation, have been embraced to compress LLMs, targeting…

Artificial Intelligence · Computer Science 2024-11-01 Xuan Shen , Pu Zhao , Yifan Gong , Zhenglun Kong , Zheng Zhan , Yushu Wu , Ming Lin , Chao Wu , Xue Lin , Yanzhi Wang

Large Language Models (LLMs) have demonstrated remarkable improvements in reasoning and planning through increased test-time compute, often by framing problem-solving as a search process. While methods like Monte Carlo Tree Search (MCTS)…

Artificial Intelligence · Computer Science 2025-06-06 Nathan Herr , Tim Rocktäschel , Roberta Raileanu

Large language models (LLMs) have achieved remarkable multi-step reasoning capabilities across various domains. However, LLMs still face distinct challenges in complex logical reasoning, as (1) proof-finding requires systematic exploration…

Computation and Language · Computer Science 2025-09-16 Kang He , Kaushik Roy

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in…

Quantitative Methods · Quantitative Biology 2024-07-09 Yiqing Shen , Zan Chen , Michail Mamalakis , Luhan He , Haiyang Xia , Tianbin Li , Yanzhou Su , Junjun He , Yu Guang Wang

Large Language Models (LLMs) have shown remarkable capabilities in reasoning, exemplified by the success of OpenAI-o1 and DeepSeek-R1. However, integrating reasoning with external search processes remains challenging, especially for complex…

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Designing protein sequences that fold into a target 3D structure, known as protein inverse folding, is a fundamental challenge in protein engineering. While recent deep learning methods have achieved impressive performance by recovering…

Biomolecules · Quantitative Biology 2025-06-03 Mengdi Liu , Xiaoxue Cheng , Zhangyang Gao , Hong Chang , Cheng Tan , Shiguang Shan , Xilin Chen

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

Efficient multi-hop reasoning requires Large Language Models (LLMs) based agents to acquire high-value external knowledge iteratively. Previous work has explored reinforcement learning (RL) to train LLMs to perform search-based document…

Computation and Language · Computer Science 2025-05-27 Ziliang Wang , Xuhui Zheng , Kang An , Cijun Ouyang , Jialu Cai , Yuhang Wang , Yichao Wu

Recent methodologies in LLM self-training mostly rely on LLM generating responses and filtering those with correct output answers as training data. This approach often yields a low-quality fine-tuning training set (e.g., incorrect plans or…

Computation and Language · Computer Science 2024-11-19 Dan Zhang , Sining Zhoubian , Ziniu Hu , Yisong Yue , Yuxiao Dong , Jie Tang
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