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Protein-DNA interactions are vital for many processes in living cells, especially transcriptional regulation and DNA modification. To further our understanding of these important processes on the microscopic level, it is necessary that…

Biomolecules · Quantitative Biology 2007-05-23 Jason E Donald , William W Chen , Eugene I Shakhnovich

Retrosynthesis -- the process of identifying a set of reactants to synthesize a target molecule -- is of vital importance to material design and drug discovery. Existing machine learning approaches based on language models and graph neural…

Chemical Physics · Physics 2021-12-10 Ruoxi Sun , Hanjun Dai , Li Li , Steven Kearnes , Bo Dai

With the advent of score-matching techniques for model training and Langevin dynamics for sample generation, energy-based models (EBMs) have gained renewed interest as generative models. Recent EBMs usually use neural networks to define…

Machine Learning · Computer Science 2025-05-05 Yukun Li , Li-Ping Liu

The protein folding problem has been fundamentally transformed by artificial intelligence, evolving from static structure prediction toward the modeling of dynamic conformational ensembles and complex biomolecular interactions. This review…

Computer Vision and Pattern Recognition · Computer Science 2026-03-20 Jingzhi Chen , Lijian Xu

RNA function is tied to secondary structure, operating through dynamic and heterogeneous structural ensembles. While current analysis tools typically output single static structures or averaged contact maps, chemical probing methods like…

Biomolecules · Quantitative Biology 2026-05-20 Giuseppe Sacco , Jianhui Li , Redmond P. Smyth , Guido Sanguinetti , Giovanni Bussi

The analysis of the three-dimensional structure of proteins is an important topic in molecular biochemistry. Structure plays a critical role in defining the function of proteins and is more strongly conserved than amino acid sequence over…

Applications · Statistics 2015-01-19 Abel Rodriguez , Scott C. Schmidler

Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Quantitative Methods · Quantitative Biology 2012-07-12 Alan Lapedes , Bertrand Giraud , Christopher Jarzynski

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

The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co--evolving proteins by means of an inverse…

Biomolecules · Quantitative Biology 2015-06-16 Sara Lui , Guido Tiana

Generating novel and functional protein sequences is critical to a wide range of applications in biology. Recent advancements in conditional diffusion models have shown impressive empirical performance in protein generation tasks. However,…

Machine Learning · Computer Science 2025-12-04 Zinan Ling , Yi Shi , Brett McKinney , Da Yan , Yang Zhou , Bo Hui

Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…

Statistical Mechanics · Physics 2026-05-11 Souvik Mondal , Michael A. Sauer , Matthias Heyden

Proteins and other macromolecules exist not in a single state but as dynamic ensembles of interconverting conformations, which are essential for catalysis, allosteric regulation, and molecular recognition. While AI-based structure…

Biomolecules · Quantitative Biology 2025-10-22 Stephanie A. Wankowicz , Massimiliano Bonomi

Energy-based models (EBMs) have experienced a resurgence within machine learning in recent years, including as a promising alternative for probabilistic regression. However, energy-based regression requires a proposal distribution to be…

Machine Learning · Computer Science 2023-11-08 Fredrik K. Gustafsson , Martin Danelljan , Thomas B. Schön

Energy-based models (EBMs) are generative models that are usually trained via maximum likelihood estimation. This approach becomes challenging in generic situations where the trained energy is non-convex, due to the need to sample the Gibbs…

Machine Learning · Computer Science 2022-02-16 Carles Domingo-Enrich , Alberto Bietti , Marylou Gabrié , Joan Bruna , Eric Vanden-Eijnden

Text-to-image diffusion models have shown great success in generating high-quality text-guided images. Yet, these models may still fail to semantically align generated images with the provided text prompts, leading to problems like…

Computer Vision and Pattern Recognition · Computer Science 2024-10-10 Yasi Zhang , Peiyu Yu , Ying Nian Wu

The exponential moving average (EMA) is a commonly used statistic for providing stable estimates of stochastic quantities in deep learning optimization. Recently, EMA has seen considerable use in generative models, where it is computed with…

Machine Learning · Computer Science 2023-10-24 Jonathan Patsenker , Henry Li , Yuval Kluger

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequence representation learning methods based on Protein Language Models (PLMs) excel in sequence-based…

Quantitative Methods · Quantitative Biology 2023-10-19 Zuobai Zhang , Chuanrui Wang , Minghao Xu , Vijil Chenthamarakshan , Aurélie Lozano , Payel Das , Jian Tang

Sequences of nucleotides (for DNA and RNA) or amino acids (for proteins) are central objects in biology. Among the most important computational problems is that of sequence alignment, i.e. arranging sequences from different organisms in…

Quantitative Methods · Quantitative Biology 2020-12-08 Anna Paola Muntoni , Andrea Pagnani , Martin Weigt , Francesco Zamponi