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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 increasingly used as decision-support tools in data-constrained scientific workflows, where correctness and validity are critical. However, evaluation practices often emphasize stability or reproducibility…

Machine Learning · Computer Science 2026-03-18 Nazia Riasat

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

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

We explore optimally training protein language models, an area of significant interest in biological research where guidance on best practices is limited. Most models are trained with extensive compute resources until performance gains…

Machine Learning · Computer Science 2024-11-05 Xingyi Cheng , Bo Chen , Pan Li , Jing Gong , Jie Tang , Le Song

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

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

Molecular dynamics (MD) is a powerful approach for modelling molecular systems, but it remains computationally intensive on spatial and time scales of many macromolecular systems of biological interest. To explore the opportunities offered…

Biomolecules · Quantitative Biology 2025-08-07 Mhd Hussein Murtada , Z. Faidon Brotzakis , Michele Vendruscolo

Data in biology is redundant, noisy, and sparse. How does the type and scale of available data impact model performance? In this work, we specifically investigate how protein language models (pLMs) scale with increasing pretraining data. We…

Quantitative Methods · Quantitative Biology 2025-07-31 Aviv Spinner , Erika DeBenedictis , Corey M. Hudson

Large language models have made remarkable progress in the field of molecular science, particularly in understanding and generating functional small molecules. This success is largely attributed to the effectiveness of molecular…

Biomolecules · Quantitative Biology 2025-03-14 Zicheng Ma , Chuanliu Fan , Zhicong Wang , Zhenyu Chen , Xiaohan Lin , Yanheng Li , Shihao Feng , Jun Zhang , Ziqiang Cao , Yi Qin Gao

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have…

Quantitative Methods · Quantitative Biology 2024-01-29 Dexiong Chen , Philip Hartout , Paolo Pellizzoni , Carlos Oliver , Karsten Borgwardt

Modern Protein Language Models (PLMs) apply transformer-based model architectures from natural language processing to biological sequences, predicting a variety of protein functions and properties. However, protein language has key…

Machine Learning · Computer Science 2026-02-25 Anna Hart , Chi Han , Jeonghwan Kim , Huimin Zhao , Heng Ji

The classification of genetic variants, particularly Variants of Uncertain Significance (VUS), poses a significant challenge in clinical genetics and precision medicine. Large Language Models (LLMs) have emerged as transformative tools in…

We introduce a machine learning approach for extracting fine-grained representations of protein evolution from molecular dynamics datasets. Metastable switching linear dynamical systems extend standard switching models with a…

Machine Learning · Statistics 2016-10-07 Bharath Ramsundar , Vijay S. Pande

Large Language Models (LLMs) are being applied in a wide array of settings, well beyond the typical language-oriented use cases. In particular, LLMs are increasingly used as a plug-and-play method for fitting data and generating…

Machine Learning · Computer Science 2025-10-29 Hejia Liu , Mochen Yang , Gediminas Adomavicius

Large Language models (LLMs) have emerged as powerful tools for addressing challenges across diverse domains. Notably, recent studies have demonstrated that large language models significantly enhance the efficiency of biomolecular analysis…

Computation and Language · Computer Science 2025-03-07 Jiyue Jiang , Zikang Wang , Yuheng Shan , Heyan Chai , Jiayi Li , Zixian Ma , Xinrui Zhang , Yu Li

In this study, we expand upon the FLIP benchmark-designed for evaluating protein fitness prediction models in small, specialized prediction tasks-by assessing the performance of state-of-the-art large protein language models, including…

Machine Learning · Computer Science 2025-01-31 Manuel F. Mollon , Joaquin Gonzalez-Rodriguez , Alicia Lozano-Diez , Daniel Ramos , Doroteo T. Toledano

While protein language models (pLMs) have transformed biological research, the scaling laws governing their improvement remain underexplored. By adapting methodologies from NLP scaling laws, we investigated the optimal ratio between model…

Biomolecules · Quantitative Biology 2024-06-27 Yaiza Serrano , Álvaro Ciudad , Alexis Molina

Understanding how residue variations affect protein stability is crucial for designing functional proteins and deciphering the molecular mechanisms underlying disease-related mutations. Recent advances in protein language models (PLMs) have…

Protein language models (pLMs) produce per-residue representations that capture evolutionary and structural information, yet their mean-pooled sequence embeddings are not explicitly trained to reflect functional, evolutionary or structural…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Oriel Perets , Michal Linial , Nadav Rappoport