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Supervised fine-tuning (SFT) is a standard approach for adapting large language models to specialized domains, yet its application to protein sequence modeling and protein language models (PLMs) remains ad hoc. This is in part because…

Machine Learning · Computer Science 2025-12-11 Amin Tavakoli , Raswanth Murugan , Ozan Gokdemir , Arvind Ramanathan , Frances Arnold , Anima Anandkumar

Sequence generation applications require satisfying semantic constraints, such as ensuring that programs are correct, using certain keywords, or avoiding undesirable content. Language models, whether fine-tuned or prompted with few-shot…

Computation and Language · Computer Science 2022-11-02 Sean Welleck , Ximing Lu , Peter West , Faeze Brahman , Tianxiao Shen , Daniel Khashabi , Yejin Choi

Generating as diverse molecules as possible with desired properties is crucial for drug discovery research, which invokes many approaches based on deep generative models today. Despite recent advancements in these models, particularly in…

Machine Learning · Computer Science 2024-07-17 Changhun Lee , Gyumin Lee

Interlingua based Machine Translation (MT) aims to encode multiple languages into a common linguistic representation and then decode sentences in multiple target languages from this representation. In this work we explore this idea in the…

Computation and Language · Computer Science 2016-06-16 Amrita Saha , Mitesh M. Khapra , Sarath Chandar , Janarthanan Rajendran , Kyunghyun Cho

Large language models (LLMs) have shown promise in various natural language processing tasks, including their application to proteomics data to classify protein fragments. In this study, we curated a limited mass spectrometry dataset with…

Quantitative Methods · Quantitative Biology 2025-02-28 Taylor A Phillips , Alejandro W. Huskey , Patrick T. Huskey , Seth L. Robia , Peter M. Kekenes-Huskey

A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that…

Machine Learning · Computer Science 2023-04-10 Patrick Emami , Aidan Perreault , Jeffrey Law , David Biagioni , Peter C. St. John

Protein evolution through amino acid mutations is a cornerstone of life sciences. Recent advances in protein language models have shown rich evolutionary patterns, offering unprecedented potential for in-silicon directed evolution. However,…

Artificial Intelligence · Computer Science 2026-01-08 Yaodong Yang , Yang Wang , Jinpeng Li , Pei Guo , Da Han , Guangyong Chen , Pheng-Ann Heng

Generating novel and functional protein sequences is critical to a wide range of applications in biology. Recent advancements in conditional diffusion models have shown impressive empirical performance in protein generation tasks. However,…

Machine Learning · Computer Science 2025-12-04 Zinan Ling , Yi Shi , Brett McKinney , Da Yan , Yang Zhou , Bo Hui

Self-supervised training of language models (LMs) has seen great success for protein sequences in learning meaningful representations and for generative drug design. Most protein LMs are based on the Transformer architecture trained on…

Biomolecules · Quantitative Biology 2025-04-03 Yingheng Wang , Zichen Wang , Gil Sadeh , Luca Zancato , Alessandro Achille , George Karypis , Huzefa Rangwala

Autoregressive models have transformed protein engineering by enabling the generation of novel protein sequences beyond those found in nature. However, their sequential inference introduces significant latency, limiting their utility in…

Machine Learning · Computer Science 2025-09-29 Thomas Walton , Darin Tsui , Aryan Musharaf , Amirali Aghazadeh

Proteins play essential roles in nature, from catalyzing biochemical reactions to binding specific targets. Advances in protein engineering have the potential to revolutionize biotechnology and healthcare by designing proteins with tailored…

Biomolecules · Quantitative Biology 2025-05-05 Hocheol Lim , Geon-Ho Lee , Kyoung Tai No

Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

While deep generative models show promise for learning inverse protein folding directly from data, the lack of publicly available structure-sequence pairings limits their generalization. Previous improvements and data augmentation efforts…

Artificial Intelligence · Computer Science 2024-07-23 Jiangbin Zheng , Stan Z. Li

The remarkable mechanical properties of spider silk, including its tensile strength and extensibility, are primarily governed by the repetitive regions of the proteins that constitute the fiber, the major ampullate spidroins (MaSps).…

Machine Learning · Computer Science 2025-10-23 Neeru Dubey , Elin Karlsson , Miguel Angel Redondo , Johan Reimegård , Anna Rising , Hedvig Kjellström

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from…

Biomolecules · Quantitative Biology 2023-10-19 Xiaomin Fang , Fan Wang , Lihang Liu , Jingzhou He , Dayong Lin , Yingfei Xiang , Xiaonan Zhang , Hua Wu , Hui Li , Le Song

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM…

Biomolecules · Quantitative Biology 2023-10-06 Zeyuan Wang , Qiang Zhang , Keyan Ding , Ming Qin , Xiang Zhuang , Xiaotong Li , Huajun 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

In this paper we present a generative model for protein contact networks. The soundness of the proposed model is investigated by focusing primarily on mesoscopic properties elaborated from the spectra of the graph Laplacian. To complement…

Biomolecules · Quantitative Biology 2015-07-30 Lorenzo Livi , Enrico Maiorino , Alessandro Giuliani , Antonello Rizzi , Alireza Sadeghian

Protein sequence generation via stochastic attention produces plausible family members from small alignments without training, but treats all stored sequences equally and cannot direct generation toward a functional subset of interest. We…

Machine Learning · Computer Science 2026-03-23 Jeffrey D. Varner