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Accurately modeling and designing protein complex structures is a central problem in computational structural biology, with broad implications for understanding cellular function and developing therapeutics. This thesis investigates two…

Machine Learning · Computer Science 2026-05-13 Ziwei Xie

Background:Typically, proteins perform key biological functions by interacting with each other. As a consequence, predicting which protein pairs interact is a fundamental problem. Experimental methods are slow, expensive, and may be error…

Biomolecules · Quantitative Biology 2022-02-08 Leonardo Martini , Adriano Fazzone , Luca Becchetti

Protein structure prediction remains to be an open problem in bioinformatics. There are two main categories of methods for protein structure prediction: Free Modeling (FM) and Template Based Modeling (TBM). Protein threading, belonging to…

Biomolecules · Quantitative Biology 2015-09-14 Haicang Zhang , Mingfu Shao , Chao Wang , Jianwei Zhu , Wei-Mou Zheng , Dongbo Bu

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its…

Biomolecules · Quantitative Biology 2024-02-09 Zuobai Zhang , Jiarui Lu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang

Cryo-electron microscopy (cryo-EM) has revolutionized experimental protein structure determination. Despite advances in high resolution reconstruction, a majority of cryo-EM experiments provide either a single state of the studied…

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Automated identification of protein conformational states from simulation of an ensemble of structures is a hard problem because it requires teaching a computer to recognize shapes. We adapt the naive Bayes classifier from the machine…

Computational Physics · Physics 2020-12-02 David M. Rogers

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale,…

Computer Vision and Pattern Recognition · Computer Science 2023-08-08 Weijie Chen , Xinyan Wang , Yuhang Wang

The seminal breakthrough of AlphaFold in protein structure prediction relied on a learned potential energy function parameterized by deep models, in contrast to its successors AlphaFold2 and AlphaFold3, which lack an explicit probabilistic…

Machine Learning · Computer Science 2026-04-28 Thomas Hamelryck , Kanti V. Mardia

Recent advances in generative modeling show that pretrained representations can improve generation as conditioning features or alignment targets. Motivated by this, we study protein representations for predicting structures beyond…

Biomolecules · Quantitative Biology 2026-05-27 Taewon Kim , Hyosoon Jang , Hyunjin Seo , Seonghwan Seo , Hyeongwoo Kim , Wonho Zhung , Mingyeong Shin , Wooyoun Kim , Sungsoo Ahn

Recently developed deep learning techniques have significantly improved the accuracy of various speech and image recognition systems. In this paper we adapt some of these techniques for protein secondary structure prediction. We first train…

Machine Learning · Computer Science 2016-11-07 Akosua Busia , Jasmine Collins , Navdeep Jaitly

Protein contacts provide key information for the understanding of protein structure and function, and therefore contact prediction from sequences is an important problem. Recent research shows that some correctly predicted long-range…

Quantitative Methods · Quantitative Biology 2020-09-02 Siqi Sun

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

Understanding protein solubility is essential for their functional applications. Computational methods for predicting protein solubility are crucial for reducing experimental costs and enhancing the efficiency and success rates of protein…

Quantitative Methods · Quantitative Biology 2024-07-01 Yang Tan , Jia Zheng , Liang Hong , Bingxin Zhou

Protein-Protein Interactions (PPIs) perform essential roles in biological functions. Although some experimental techniques have been developed to detect PPIs, they suffer from high false positive and high false negative rates. Consequently,…

Quantitative Methods · Quantitative Biology 2017-12-29 Samaneh Aghajanbaglo , Sobhan Moosavi , Maseud Rahgozar , Amir Rahimi

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 structure prediction models are now capable of generating accurate 3D structural hypotheses from sequence alone. However, they routinely fail to capture the conformational diversity of dynamic biomolecular complexes, often requiring…

Machine Learning · Computer Science 2025-12-02 Rishwanth Raghu , Axel Levy , Gordon Wetzstein , Ellen D. Zhong

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola
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