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How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

Recent advances in Artificial Intelligence have enabled multi-modal systems to model and translate diverse information spaces. Extending beyond text and vision, we introduce OneProt, a multi-modal AI for proteins that integrates structural,…

Protein structural classification (PSC) is a supervised problem of assigning proteins into pre-defined structural (e.g., CATH or SCOPe) classes based on the proteins' sequence or 3D structural features. We recently proposed PSC approaches…

Molecular Networks · Quantitative Biology 2021-05-18 Khalique Newaz , Jacob Piland , Patricia L. Clark , Scott J. Emrich , Jun Li , Tijana Milenkovic

Multistate models offer a powerful framework for studying disease processes and can be used to formulate intensity-based and more descriptive marginal regression models. They also represent a natural foundation for the construction of joint…

We present InvMSAFold, an inverse folding method for generating protein sequences that is optimized for diversity and speed. For a given structure, InvMSAFold generates the parameters of a probability distribution over the space of…

Quantitative Methods · Quantitative Biology 2025-05-30 Luca Alessandro Silva , Barthelemy Meynard-Piganeau , Carlo Lucibello , Christoph Feinauer

Multi-plane light converter (MPLC) designs supporting hundreds of modes are attractive in high-throughput optical communications. These photonic structures typically comprise >10 phase masks in free space, with millions of independent…

Signal Processing · Electrical Eng. & Systems 2023-04-14 Zheyuan Zhu , Joe H. Doerr , Guifang Li , Shuo Pang

Protein dynamics underlie many biological functions, yet remain difficult to characterize due to the high computational cost of molecular dynamics simulations and the scarcity of dynamic structural data. This survey reviews recent advances…

Biomolecules · Quantitative Biology 2026-04-29 Haocheng Tang , Liang Shi , Ya-Shi Zhang , Xixian Liu , Jian Tang , Jiarui Lu

The inapplicability of amino acid covariation methods to small protein families has limited their use for structural annotation of whole genomes. Recently, deep learning has shown promise in allowing accurate residue-residue contact…

Biomolecules · Quantitative Biology 2019-09-10 Joe G Greener , Shaun M Kandathil , David T Jones

Protein folding produces characteristic and functional three-dimensional structures from unfolded polypeptides or disordered coils. The emergence of extraordinary complexity in the protein folding process poses astonishing challenges to…

Biomolecules · Quantitative Biology 2013-08-14 Kelin Xia , Guo-Wei Wei

Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…

Computational Physics · Physics 2018-12-05 Dan Mendels , Giovannimaria Piccini , Z. Faidon Brotzakis , Yi I. Yang , Michele Parrinello

Recent advances in de novo protein binder design have enabled increasing experimental validation, yet reported in silico metrics remain difficult to interpret or compare across studies due to non-standardized evaluation protocols. We…

Quantitative Methods · Quantitative Biology 2026-05-25 Cong Liu , Milong Ren , Jiaqi Guan , Chengyue Gong , Jinyuan Sun , Xinshi Chen , Wenzhi Xiao

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Biomolecules · Quantitative Biology 2018-04-18 David Menéndez Hurtado , Karolis Uziela , Arne Elofsson

Motivation: RNA design aims to find RNA sequences that fold into a given target secondary structure, a problem also known as RNA inverse folding. However, not all target structures are designable. Recent advances in RNA designability have…

Data Structures and Algorithms · Computer Science 2026-04-28 Tianshuo Zhou , David H. Mathews , Liang Huang

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…

We present a new model, Predictive State Recurrent Neural Networks (PSRNNs), for filtering and prediction in dynamical systems. PSRNNs draw on insights from both Recurrent Neural Networks (RNNs) and Predictive State Representations (PSRs),…

Machine Learning · Statistics 2017-06-20 Carlton Downey , Ahmed Hefny , Boyue Li , Byron Boots , Geoffrey Gordon

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

The biological properties of proteins are uniquely determined by their structure and dynamics. A protein in solution populates a structural ensemble of metastable configurations around the global fold. From overall rotation to local…

Biological Physics · Physics 2015-12-09 J. Copperman , M. G. Guenza

Intrinsically disordered proteins (IDPs) constitute a broad set of proteins with few uniting and many diverging properties. IDPs-and intrinsically disordered regions (IDRs) interspersed between folded domains-are generally characterized as…

Biomolecules · Quantitative Biology 2021-06-03 Kresten Lindorff-Larsen , Birthe B. Kragelund
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