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Predicting the functional impact of single amino acid substitutions (SAVs) is central to understanding genetic disease and engineering therapeutic proteins. While protein language models and structure-based methods have achieved strong…

Machine Learning · Computer Science 2026-04-15 Seungik Cho

AlphaFold is a neural-network-based tool for the prediction of 3D structures of protein. In CASP14, a blind structure prediction challenge, it performed significantly better than other competitors, which makes it the best available…

Biomolecules · Quantitative Biology 2022-06-22 Vojtěch Spiwok , Martin Kurečka , Aleš Křenek

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…

Populations and Evolution · Quantitative Biology 2013-12-04 Andrew J. Bordner , Hans D. Mittelmann

We introduce IntFold, a controllable foundation model for general and specialized biomolecular structure prediction. Utilizing a high-performance custom attention kernel, IntFold achieves accuracy comparable to the state-of-the-art…

Biomolecules · Quantitative Biology 2025-07-08 The IntFold Team , Leon Qiao , Wayne Bai , He Yan , Gary Liu , Nova Xi , Xiang Zhang , Siqi Sun

Transformer architectures have proven to learn useful representations for protein classification and generation tasks. However, these representations present challenges in interpretability. In this work, we demonstrate a set of methods for…

Computation and Language · Computer Science 2021-03-30 Jesse Vig , Ali Madani , Lav R. Varshney , Caiming Xiong , Richard Socher , Nazneen Fatema Rajani

Multilinear transformations are key in high-performance computing (HPC) and artificial intelligence (AI) workloads, where data is represented as tensors. However, their high computational and memory demands, which grow with dimensionality,…

Distributed, Parallel, and Cluster Computing · Computer Science 2025-07-01 Stanislav Sedukhin , Yoichi Tomioka , Kazuya Matsumoto , Yuichi Okuyama

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them…

Quantitative Methods · Quantitative Biology 2024-12-10 Bo Chen , Xingyi Cheng , Pan Li , Yangli-ao Geng , Jing Gong , Shen Li , Zhilei Bei , Xu Tan , Boyan Wang , Xin Zeng , Chiming Liu , Aohan Zeng , Yuxiao Dong , Jie Tang , Le Song

The 2024 Nobel Prize in Chemistry was awarded in part for protein structure prediction using AlphaFold2, an artificial intelligence/machine learning (AI/ML) model trained on vast amounts of sequence and 3D structure data. AlphaFold2 and…

Biomolecules · Quantitative Biology 2025-04-22 Alexander M. Ille , Emily Anas , Michael B. Mathews , Stephen K. Burley

Recent advancements in deep learning for predicting 3D protein structures have shown promise, particularly when leveraging inputs like protein sequences and Cryo-Electron microscopy (Cryo-EM) images. However, these techniques often fall…

Computer Vision and Pattern Recognition · Computer Science 2024-08-13 Jaydeep Rade , Ethan Herron , Soumik Sarkar , Anwesha Sarkar , Adarsh Krishnamurthy

Time series forecasting is widely used in extensive applications, such as traffic planning and weather forecasting. However, real-world time series usually present intricate temporal variations, making forecasting extremely challenging.…

Machine Learning · Computer Science 2024-05-24 Shiyu Wang , Haixu Wu , Xiaoming Shi , Tengge Hu , Huakun Luo , Lintao Ma , James Y. Zhang , Jun Zhou

Although machine learning has transformed protein structure prediction of folded protein ground states with remarkable accuracy, intrinsically disordered proteins and regions (IDPs/IDRs) are defined by diverse and dynamical structural…

Biomolecules · Quantitative Biology 2025-04-01 Oufan Zhang , Zi Hao Liu , Julie D Forman-Kay , Teresa Head-Gordon

Synthetic sequence-controlled polymers promise to transform polymer science by combining the chemical versatility of synthetic polymers with the precise sequence-mediated functionality of biological proteins. However, design of these…

Materials Science · Physics 2025-07-30 Md Mushfiqul Islam , Nishat N. Labiba , Lawrence O. Hall , David S. Simmons

Structure-based drug discovery, encompassing the tasks of protein-ligand docking and pocket-aware 3D drug design, represents a core challenge in drug discovery. However, no existing work can deal with both tasks to effectively leverage the…

Computational Engineering, Finance, and Science · Computer Science 2025-02-10 Xiuyuan Hu , Guoqing Liu , Can Chen , Yang Zhao , Hao Zhang , Xue Liu

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

Designing proteins with desired functions or properties represents a core goal in synthetic biology and drug discovery. Recent advances in protein language models (PLMs) have enabled the generation of highly designable protein sequences,…

Machine Learning · Computer Science 2026-05-12 Yulin Zhang , He Cao , Zihao Jiang , Chenyi Zi , Zhipeng Zhou , Zijing Liu , Yu Li , Jia Li , Ziqi Gao

Deep neural networks such as AlphaFold and RoseTTAFold predict remarkably accurate structures of proteins compared to other algorithmic approaches. It is known that biologically small perturbations in the protein sequence do not lead to…

Biomolecules · Quantitative Biology 2021-09-21 Sumit Kumar Jha , Arvind Ramanathan , Rickard Ewetz , Alvaro Velasquez , Susmit Jha

Structure-informed protein representation learning is essential for effective protein function annotation and \textit{de novo} design. However, the presence of inherent noise in both crystal and AlphaFold-predicted structures poses…

Biomolecules · Quantitative Biology 2025-03-25 Zhongyue Zhang , Runze Ma , Yanjie Huang , Shuangjia Zheng

Real-world problems are often dependent on multiple data modalities, making multimodal fusion essential for leveraging diverse information sources. In high-stakes domains, such as in healthcare, understanding how each modality contributes…

Neural and Evolutionary Computing · Computer Science 2025-05-19 Mafalda Malafaia , Thalea Schlender , Tanja Alderliesten , Peter A. N. Bosman

Protein (receptor)--ligand interaction prediction is a critical component in computer-aided drug design, significantly influencing molecular docking and virtual screening processes. Despite the development of numerous scoring functions in…

Biomolecules · Quantitative Biology 2024-01-22 Haoyu Lin , Shiwei Wang , Jintao Zhu , Yibo Li , Jianfeng Pei , Luhua Lai

Optical multilayer thin-films are fundamental components that enable the precise control of reflectance, transmittance, and phase shift in the design of photonic systems. Rapid and accessible simulation of these structures holds critical…

Computational Physics · Physics 2025-10-27 Bahrem Serhat Danis , Esra Zayim