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Recent years have witnessed a surge in the development of protein structural tokenization methods, which chunk protein 3D structures into discrete or continuous representations. Structure tokenization enables the direct application of…

Quantitative Methods · Quantitative Biology 2025-06-26 Xinyu Yuan , Zichen Wang , Marcus Collins , Huzefa Rangwala

Background: The inception of next generations sequencing technologies have exponentially increased the volume of biological sequence data. Protein sequences, being quoted as the `language of life', has been analyzed for a multitude of…

Quantitative Methods · Quantitative Biology 2020-12-08 Nabil Ibtehaz , S. M. Shakhawat Hossain Sourav , Md. Shamsuzzoha Bayzid , M. Sohel Rahman

Spoken language understanding is typically based on pipeline architectures including speech recognition and natural language understanding steps. These components are optimized independently to allow usage of available data, but the overall…

Audio and Speech Processing · Electrical Eng. & Systems 2020-08-13 Pavel Denisov , Ngoc Thang Vu

Predicting protein properties such as solvent accessibility and secondary structure from its primary amino acid sequence is an important task in bioinformatics. Recently, a few deep learning models have surpassed the traditional window…

Machine Learning · Computer Science 2016-05-11 Zeming Lin , Jack Lanchantin , Yanjun Qi

We theorize that phylogenetic profiles provide a quantitative method that can relate the structural and functional properties of proteins, as well as their evolutionary relationships. A key feature of phylogenetic profiles is the…

Quantitative Methods · Quantitative Biology 2009-11-04 Yoojin Hong , Jaewoo Kang , Dongwon Lee , Randen L. Patterson , Damian B. van Rossum

We investigate the capability of a transformer pretrained on natural language to generalize to other modalities with minimal finetuning -- in particular, without finetuning of the self-attention and feedforward layers of the residual…

Machine Learning · Computer Science 2021-07-01 Kevin Lu , Aditya Grover , Pieter Abbeel , Igor Mordatch

Compound-Protein Interaction (CPI) prediction aims to predict the pattern and strength of compound-protein interactions for rational drug discovery. Existing deep learning-based methods utilize only the single modality of protein sequences…

Biomolecules · Quantitative Biology 2024-02-14 Lirong Wu , Yufei Huang , Cheng Tan , Zhangyang Gao , Bozhen Hu , Haitao Lin , Zicheng Liu , Stan Z. 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

Identifying interactions between proteins is important to understand underlying biological processes. Extracting a protein-protein interaction (PPI) from the raw text is often very difficult. Previous supervised learning methods have used…

Quantitative Methods · Quantitative Biology 2018-08-10 Mahtab Ahmed , Jumayel Islam , Muhammad Rifayat Samee , Robert E. Mercer

Protein representation learning is critical for numerous biological tasks. Recently, large transformer-based protein language models (pLMs) pretrained on large scale protein sequences have demonstrated significant success in sequence-based…

Machine Learning · Computer Science 2025-08-12 Xuefeng Liu , Songhao Jiang , Chih-chan Tien , Jinbo Xu , Rick Stevens

Protein-nucleic acid interactions play a very important role in a variety of biological activities. Accurate identification of nucleic acid-binding residues is a critical step in understanding the interaction mechanisms. Although many…

Quantitative Methods · Quantitative Biology 2024-01-23 Wenwu Zeng , Dafeng Lv , Wenjuan Liu , Shaoliang Peng

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

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

Prediction suffix trees (PST) provide an effective tool for sequence modelling and prediction. Current prediction techniques for PSTs rely on exact matching between the suffix of the current sequence and the previously observed sequence. We…

Machine Learning · Computer Science 2018-08-08 Dongwoo Kim , Christian Walder

Is there a foreign language describing protein sequences and structures simultaneously? Protein structures, represented by continuous 3D points, have long posed a challenge due to the contrasting modeling paradigms of discrete sequences. To…

Computational Engineering, Finance, and Science · Computer Science 2023-10-10 Zhangyang Gao , Cheng Tan , Stan Z. Li

Multimodal protein language models (PLMs) integrate sequence and token-based structural information, serving as a powerful foundation for protein modeling, generation, and design. However, the reliance on tokenizing 3D structures into…

Machine Learning · Computer Science 2025-06-13 Cheng-Yen Hsieh , Xinyou Wang , Daiheng Zhang , Dongyu Xue , Fei Ye , Shujian Huang , Zaixiang Zheng , Quanquan Gu

A syntactic language model (SLM) incrementally generates a sentence with its syntactic tree in a left-to-right manner. We present Generative Pretrained Structured Transformers (GPST), an unsupervised SLM at scale capable of being…

Computation and Language · Computer Science 2024-06-18 Xiang Hu , Pengyu Ji , Qingyang Zhu , Wei Wu , Kewei Tu

This paper investigates the application of the transformer architecture in protein folding, as exemplified by DeepMind's AlphaFold project, and its implications for the understanding of so-called large language models. The prevailing…

Computers and Society · Computer Science 2024-12-10 Fabian Offert , Paul Kim , Qiaoyu Cai

Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel…

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