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For many macromolecular systems the accurate sampling of the relevant regions on the potential energy surface cannot be obtained by a single, long Molecular Dynamics (MD) trajectory. New approaches are required to promote more efficient…

Computational Engineering, Finance, and Science · Computer Science 2016-06-02 Vivekanandan Balasubramanian , Iain Bethune , Ardita Shkurti , Elena Breitmoser , Eugen Hruska , Cecilia Clementi , Charles Laughton , Shantenu Jha

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

Molecular dynamics (MD) simulations are useful in obtaining thermodynamic and kinetic properties of bio-molecules but are limited by the timescale barrier, i.e., we may be unable to efficiently obtain properties because we need to run…

Chemical Physics · Physics 2017-08-23 Surl-Hee Ahn , Jay W. Grate , Eric F. Darve

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

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

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

One of the key limitations of Molecular Dynamics simulations is the computational intractability of sampling protein conformational landscapes associated with either large system size or long timescales. To overcome this bottleneck, we…

Biomolecules · Quantitative Biology 2018-07-09 Zahra Shamsi , Kevin J. Cheng , Diwakar Shukla

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

Biomolecules · Quantitative Biology 2019-08-02 Heng Ma , Debsindhu Bhowmik , Hyungro Lee , Matteo Turilli , Michael T. Young , Shantenu Jha , Arvind Ramanathan

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

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

Understanding the principles of protein folding is a cornerstone of computational biology, with implications for drug design, bioengineering, and the understanding of fundamental biological processes. Lattice protein folding models offer a…

Disordered Systems and Neural Networks · Physics 2025-08-08 Shoummo Ahsan Khandoker , Estelle M. Inack , Mohamed Hibat-Allah

Task robust adaptation is a long-standing pursuit in sequential decision-making. Some risk-averse strategies, e.g., the conditional value-at-risk principle, are incorporated in domain randomization or meta reinforcement learning to…

Machine Learning · Computer Science 2025-05-16 Yun Qu , Qi Cheems Wang , Yixiu Mao , Yiqin Lv , Xiangyang Ji

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-09-18 Hyungro Lee , Heng Ma , Matteo Turilli , Debsindhu Bhowmik , Shantenu Jha , Arvind Ramanathan

The efficacy of drug treatments depends on how tightly small molecules bind to their target proteins. The rapid and accurate quantification of the strength of these interactions (as measured by binding affinity) is a grand challenge of…

Distributed, Parallel, and Cluster Computing · Computer Science 2018-10-30 Jumana Dakka , Kristof Farkas-Pall , Matteo Turilli , David W Wright , Peter V Coveney , Shantenu Jha

In adaptive-sampling control, the control frequency can be adjusted during task execution. Ensuring that these changes do not jeopardize the safety of the system being controlled requires attention. We introduce robust M-step hold model…

Systems and Control · Electrical Eng. & Systems 2026-05-08 Spencer Schutz , Charlott Vallon , Francesco Borrelli

We introduce a machine learning approach for extracting fine-grained representations of protein evolution from molecular dynamics datasets. Metastable switching linear dynamical systems extend standard switching models with a…

Machine Learning · Statistics 2016-10-07 Bharath Ramsundar , Vijay S. Pande

Interest in equilibrium-based sampling methods has grown with recent advances in computational hardware and Markov state modeling (MSM) methods, yet outstanding questions remain that hinder widespread adoption. Namely, how do sampling…

Biomolecules · Quantitative Biology 2018-05-15 Maxwell I. Zimmerman , Justin R. Porter , Xianqiang Sun , Roseane R. Silva , Gregory R. Bowman

Model Predictive Control (MPC) is a successful control methodology, which is applied to increasingly complex systems. However, real-time feasibility of MPC can be challenging for complex systems, certainly when an (extremely) large number…

Systems and Control · Electrical Eng. & Systems 2024-10-25 S. A. N. Nouwens , B. de Jager , M. M. Paulides , W. P. M. H. Heemels

Configurational entropy is an important factor in the free energy change of many macromolecular recognition and binding processes, and has been intensively studied. Despite great progresses that have been made, the global sampling remains…

Biological Physics · Physics 2012-12-04 Wenzhao Li , Kai Wang , Suyan Tian , Pu Tian

Efficient sampling in biomolecular simulations is critical for accurately capturing the complex dynamical behaviors of biological systems. Adaptive sampling techniques aim to improve efficiency by focusing computational resources on the…

Biomolecules · Quantitative Biology 2024-10-22 Hassan Nadeem , Diwakar Shukla
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