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Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Excitement at the prospect of using data-driven generative models to sample configurational ensembles of biomolecular systems stems from the extraordinary success of these models on a diverse set of high-dimensional sampling tasks. Unlike…

Statistical Mechanics · Physics 2024-02-06 Shriram Chennakesavalu , Grant M. Rotskoff

It is becoming clear that traditional, single-structure models of proteins are insufficient for understanding their biological function. Here, we outline one method for inferring, from experiments, not only the most common structure a…

Biological Physics · Physics 2014-08-04 Thomas J. Lane , Christian R. Schwantes , Kyle A. Beauchamp , Vijay S. Pande

Protein dynamics play a crucial role in protein biological functions and properties, and their traditional study typically relies on time-consuming molecular dynamics (MD) simulations conducted in silico. Recent advances in generative…

Biomolecules · Quantitative Biology 2025-06-02 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Aurélie Lozano , Vijil Chenthamarakshan , Payel Das , Jian Tang

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

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

Achieving a comprehensive understanding of the behaviour of proteins is greatly facilitated by the knowledge of their structures, thermodynamics and dynamics. All this information can be provided in an effective manner in terms of…

Quantitative Methods · Quantitative Biology 2019-03-27 Massimiliano Bonomi , Michele Vendruscolo

Inverse protein folding -- the task of predicting a protein sequence from its backbone atom coordinates -- has surfaced as an important problem in the "top down", de novo design of proteins. Contemporary approaches have cast this problem as…

Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with…

Quantitative Methods · Quantitative Biology 2022-11-22 Muyuan Chen , Bogdan Toader , Roy Lederman

Understanding the dynamic behavior of proteins is critical to elucidating their functional mechanisms, yet generating realistic, temporally coherent trajectories of protein ensembles remains a significant challenge. In this work, we…

Biomolecules · Quantitative Biology 2025-11-11 Yaoyao Xu , Di Wang , Zihan Zhou , Tianshu Yu , Mingchen Chen

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

Generative models trained on public databases of protein structures, most of which have been determined by X-ray crystallography, now provide powerful priors for structure prediction. However, they are not readily conditioned on the…

Machine Learning · Computer Science 2026-05-18 Minseo Kim , Huanghao Mai , Jay Shenoy , Alec Follmer , Gordon Wetzstein , Frederic Poitevin

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

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

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

Recent advances in deep learning have enabled the generation of realistic data by training generative models on large datasets of text, images, and audio. While these models have demonstrated exceptional performance in generating novel and…

Materials Science · Physics 2024-06-17 Izumi Takahara , Kiyou Shibata , Teruyasu Mizoguchi

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…

Populations and Evolution · Quantitative Biology 2020-09-22 Michael Golden , Eduardo García-Portugués , Michael Sørensen , Kanti V. Mardia , Thomas Hamelryck , Jotun Hein

The interaction of a protein with its environment can be understood and controlled via its 3D structure. Experimental methods for protein structure determination, such as X-ray crystallography or cryogenic electron microscopy, shed light on…

Machine Learning · Computer Science 2025-04-24 Axel Levy , Eric R. Chan , Sara Fridovich-Keil , Frédéric Poitevin , Ellen D. Zhong , Gordon Wetzstein
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