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Large Language Models (LLMs) are increasingly embedded in applications, and people can shape model behavior by editing prompt instructions. Yet encoding subtle, domain-specific policies into prompts is challenging. Although this process…

Human-Computer Interaction · Computer Science 2026-03-26 Minjae Lee , Minsuk Kahng

Large language models (LLMs) have garnered considerable attention for their proficiency in tackling intricate tasks, particularly leveraging their capacities for zero-shot and in-context learning. However, their utility has been…

Biomolecules · Quantitative Biology 2024-05-14 Yiqing Shen , Outongyi Lv , Houying Zhu , Yu Guang Wang

Proteins play a pivotal role in biological systems. The use of machine learning algorithms for protein classification can assist and even guide biological experiments, offering crucial insights for biotechnological applications. We…

Quantitative Methods · Quantitative Biology 2024-10-24 Yizheng Wang , Yixiao Zhai , Yijie Ding , Quan Zou

Generative models derived from large protein sequence alignments define complex fitness landscapes, but their utility for accurately modeling non-equilibrium evolutionary dynamics remains unclear. In this work, we perform a rigorous…

Populations and Evolution · Quantitative Biology 2026-02-10 Leonardo Di Bari , Thierry Mora , Andrea Pagnani , Aleksandra M. Walczak , Francesco Zamponi , Saverio Rossi

Motivation: Protein embedding, which represents proteins as numerical vectors, is a crucial step in various learning-based protein annotation/classification problems, including gene ontology prediction, protein-protein interaction…

Genomics · Quantitative Biology 2024-05-21 Jiayu Shang , Cheng Peng , Yongxin Ji , Jiaojiao Guan , Dehan Cai , Xubo Tang , Yanni Sun

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

We introduce a pioneering methodology for boosting large language models in the domain of protein representation learning. Our primary contribution lies in the refinement process for correlating the over-reliance on co-evolution knowledge,…

Artificial Intelligence · Computer Science 2024-12-05 Yaoyao Xu , Xinjian Zhao , Xiaozhuang Song , Benyou Wang , Tianshu Yu

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

Physiologically Based Pharmacokinetic (PBPK) modeling is a cornerstone of model-informed drug development (MIDD), providing a mechanistic framework to predict drug absorption, distribution, metabolism, and excretion (ADME). Despite its…

Machine Learning · Computer Science 2026-02-24 Shunqi Liu , Han Qiu , Tong Wang

Protein sequence design methods have demonstrated strong performance in sequence generation for de novo protein design. However, as the training objective was sequence recovery, it does not guarantee designability--the likelihood that a…

Machine Learning · Computer Science 2025-06-03 Fanglei Xue , Andrew Kubaney , Zhichun Guo , Joseph K. Min , Ge Liu , Yi Yang , David Baker

Representation learning for proteins has primarily focused on the global understanding of protein sequences regardless of their length. However, shorter proteins (known as peptides) take on distinct structures and functions compared to…

Quantitative Methods · Quantitative Biology 2022-11-15 Gil Sadeh , Zichen Wang , Jasleen Grewal , Huzefa Rangwala , Layne Price

Reparameterized diffusion models (RDMs) have recently matched autoregressive methods in protein generation, motivating their use for challenging tasks such as designing membrane proteins, which possess interleaved soluble and transmembrane…

Biomolecules · Quantitative Biology 2025-09-30 Shrey Goel , Peregrine M. Schray , Yinuo Zhang , Sophia Vincoff , Huong T. Kratochvil , Pranam Chatterjee

Accurate localization of proteins from fluorescence microscopy images is challenging due to the inter-class similarities and intra-class disparities introducing grave concerns in addressing multi-class classification problems. Conventional…

Computer Vision and Pattern Recognition · Computer Science 2021-10-11 Muhammad Tahir , Saeed Anwar , Ajmal Mian , Abdul Wahab Muzaffar

The development of powerful natural language models have increased the ability to learn meaningful representations of protein sequences. In addition, advances in high-throughput mutagenesis, directed evolution, and next-generation…

Deep generative modeling for biological sequences presents a unique challenge in reconciling the bias-variance trade-off between explicit biological insight and model flexibility. The deep manifold sampler was recently proposed as a means…

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Pre-trained protein models (PTPMs) represent a protein with one fixed embedding and thus are not capable for diverse tasks. For example, protein structures can shift, namely protein folding, between several conformations in various…

Artificial Intelligence · Computer Science 2022-02-08 Qiang Zhang , Zeyuan Wang , Yuqiang Han , Haoran Yu , Xurui Jin , Huajun Chen

Engineering new molecules with desirable functions and properties has the potential to extend our ability to engineer proteins beyond what nature has so far evolved. Advances in the so-called "de novo" design problem have recently been…

Machine Learning · Computer Science 2023-10-17 Adam Winnifrith , Carlos Outeiral , Brian Hie

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes…

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