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Much scientific enquiry across disciplines is founded upon a mechanistic treatment of dynamic systems that ties form to function. A highly visible instance of this is in molecular biology, where an important goal is to determine…

Biomolecules · Quantitative Biology 2021-06-17 Xiaojie Guo , Yuanqi Du , Sivani Tadepalli , Liang Zhao , Amarda Shehu

Molecular dynamics (MD) is a powerful technique for studying microscopic phenomena, but its computational cost has driven significant interest in the development of deep learning-based surrogate models. We introduce generative modeling of…

Biomolecules · Quantitative Biology 2024-09-27 Bowen Jing , Hannes Stärk , Tommi Jaakkola , Bonnie Berger

Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is…

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour

The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the…

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

The scarcity of experimental protein-ligand complexes poses a significant challenge for training robust deep learning models for molecular docking. Given the prohibitive cost and time constraints associated with experimental structure…

Biomolecules · Quantitative Biology 2025-09-17 Sofiene Khiari , Matthew R. Masters , Amr H. Mahmoud , Markus A. Lill

Computational protein design has the potential to deliver novel molecular structures, binders, and catalysts for myriad applications. Recent neural graph-based models that use backbone coordinate-derived features show exceptional…

Biomolecules · Quantitative Biology 2022-04-28 Alex J. Li , Vikram Sundar , Gevorg Grigoryan , Amy E. Keating

In this study, we address the challenge of using energy-based models to produce high-quality, label-specific data in complex structured datasets, such as population genetics, RNA or protein sequences data. Traditional training methods…

Machine Learning · Computer Science 2025-02-07 Alessandra Carbone , Aurélien Decelle , Lorenzo Rosset , Beatriz Seoane

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 conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu

Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended timescales. Our methodology involves simulating proteins with molecular…

Biomolecules · Quantitative Biology 2023-10-11 Carles Navarro , Maciej Majewski , Gianni de Fabritiis

Recently, diffusion- and flow-based generative models of protein structures have emerged as a powerful tool for de novo protein design. Here, we develop Proteina, a new large-scale flow-based protein backbone generator that utilizes…

Fitting generative models to sequential data typically involves two recursive computations through time, one forward and one backward. The latter could be a computation of the loss gradient (as in backpropagation through time), or an…

Machine Learning · Computer Science 2023-10-23 Azwar Abdulsalam , Joseph G. Makin

The techniques of data-driven backmapping from coarse-grained (CG) to fine-grained (FG) representation often struggle with accuracy, unstable training, and physical realism, especially when applied to complex systems such as proteins. In…

Machine Learning · Computer Science 2025-05-26 Georgios Kementzidis , Erin Wong , John Nicholson , Ruichen Xu , Yuefan Deng

Consider learning a generative model for time-series data. The sequential setting poses a unique challenge: Not only should the generator capture the conditional dynamics of (stepwise) transitions, but its open-loop rollouts should also…

Machine Learning · Statistics 2023-11-03 Daniel Jarrett , Ioana Bica , Mihaela van der Schaar

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Generating molecular dynamics (MD) trajectories using deep generative models has attracted increasing attention, yet remains inherently challenging due to the limited availability of MD data and the complexities involved in modeling…

Machine Learning · Computer Science 2026-04-07 Aniketh Iyengar , Jiaqi Han , Pengwei Sun , Mingjian Jiang , Jianwen Xie , Stefano Ermon

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

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai