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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

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

Modeling and simulating the protein folding process overall remains a grand challenge in computational biology. We systematically investigate end-to-end quantum algorithms for simulating various protein dynamics with effects, such as…

Quantum Physics · Physics 2025-04-17 Zhenning Liu , Xiantao Li , Chunhao Wang , Jin-Peng Liu

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

In the last decade, advances in molecular dynamics (MD) and Markov State Model (MSM) methodologies have made possible accurate and efficient estimation of kinetic rates and reactive pathways for complex biomolecular dynamics occurring on…

Biomolecules · Quantitative Biology 2020-01-29 Hongbin Wan , Vincent A. Voelz

Molecular dynamics (MD) simulations allow atomistic insights into chemical and biological processes. Accurate MD simulations require computationally demanding quantum-mechanical calculations, being practically limited to short timescales…

Understanding molecular structure, dynamics, and reactivity requires bridging processes that occur across widely separated time scales. Conventional molecular dynamics simulations provide atomistic resolution, but their femtosecond time…

Chemical Physics · Physics 2025-10-10 Juan Viguera Diez , Mathias Schreiner , Simon Olsson

Molecular dynamics (MD) simulation is widely used to study protein conformations and dynamics. However, conventional simulation suffers from being trapped in some local energy minima that are hard to escape. Thus, most computational time is…

Quantitative Methods · Quantitative Biology 2022-04-28 Hao Tian , Xi Jiang , Sian Xiao , Hunter La Force , Eric C. Larson , Peng Tao

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

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

A reliable prediction of 3D protein structures from sequence data remains a big challenge due to both theoretical and computational difficulties. We have previously shown that our kinetostatic compliance method (KCM) implemented into the…

Computational Engineering, Finance, and Science · Computer Science 2017-12-27 Pouya Tavousi , Morad Behandish , Horea T. Ilies , Kazem Kazerounian

Machine learning (ML) is rapidly transforming the way molecular dynamics simulations are performed and analyzed, from materials modeling to studies of protein folding and function. ML algorithms are often employed to learn low-dimensional…

Soft Condensed Matter · Physics 2025-09-23 Jayashrita Debnath , Gerhard Hummer

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

Machine learning (ML)-based steering can improve the performance of ensemble-based simulations by allowing for online selection of more scientifically meaningful computations. We present DeepDriveMD, a framework for ML-driven steering of…

Distributed, Parallel, and Cluster Computing · Computer Science 2022-07-13 Alexander Brace , Igor Yakushin , Heng Ma , Anda Trifan , Todd Munson , Ian Foster , Arvind Ramanathan , Hyungro Lee , Matteo Turilli , Shantenu Jha

We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a…

Biological Physics · Physics 2013-08-13 Jacek Wabik , Sebastian Kmiecik , Dominik Gront , Maksim Kouza , Andrzej Kolinski

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

Combining discrete and continuous data is an important capability for generative models. We present Discrete Flow Models (DFMs), a new flow-based model of discrete data that provides the missing link in enabling flow-based generative models…

Machine Learning · Statistics 2024-06-07 Andrew Campbell , Jason Yim , Regina Barzilay , Tom Rainforth , Tommi Jaakkola

Deep generative models (DGM) are neural networks with many hidden layers trained to approximate complicated, high-dimensional probability distributions using a large number of samples. When trained successfully, we can use the DGMs to…

Machine Learning · Computer Science 2021-04-13 Lars Ruthotto , Eldad Haber

The study of biomolecular folding has been greatly advanced by single-molecule force spectroscopy (SMFS), which enables the observation of the dynamics of individual molecules. However, extracting quantitative models of fundamental…

Chemical Physics · Physics 2026-04-30 Lars Dingeldein , Aaron Lyons , Pilar Cossio , Michael Woodside , Roberto Covino

Molecular dynamics (MD) simulations employing classical force fields constitute the cornerstone of contemporary atomistic modeling in chemistry, biology, and materials science. However, the predictive power of these simulations is only as…

Chemical Physics · Physics 2018-09-26 Stefan Chmiela , Huziel E. Sauceda , Klaus-Robert Müller , Alexandre Tkatchenko