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Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with…

Statistical Mechanics · Physics 2009-10-31 Leonard D. Bogarad , Michael W. Deem

We introduce a rigorous method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions for which it is possible to identify a priori a slow reaction coordinate. In…

Biomolecules · Quantitative Biology 2015-06-05 P. Faccioli , F. Pederiva

In molecular dynamics (MD) simulations, accessing transition probabilities between states is crucial for understanding kinetic information, such as reaction paths and rates. However, standard MD simulations are hindered by the capacity to…

Chemical Physics · Physics 2025-08-07 Yanbin Wang , Jakub Rydzewski , Ming Chen

This work examines the conformational ensemble involved in $\beta$-hairpin folding by means of advanced molecular dynamics simulations and dimensionality reduction. A fully atomistic description of the protein and the surrounding solvent…

Chemical Physics · Physics 2023-06-16 Albert Ardevol , Gareth A. Tribello , Michele Ceriotti , Michele Parrinello

While recent advances in AI have transformed protein structure prediction, protein function is also strongly influenced by the thermodynamic and kinetic features encoded in its underlying free-energy surface. Here, we propose a…

Biological Physics · Physics 2026-04-29 Alexander Zhilkin , Muralika Medaparambath , Dan Mendels

Protein-protein bindings play a key role in a variety of fundamental biological processes, and thus predicting the effects of amino acid mutations on protein-protein binding is crucial. To tackle the scarcity of annotated mutation data,…

Quantitative Methods · Quantitative Biology 2024-05-20 Lirong Wu , Yijun Tian , Haitao Lin , Yufei Huang , Siyuan Li , Nitesh V Chawla , Stan Z. Li

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

Molecular dynamics (MD) simulation is a widely used technique to simulate molecular systems, most commonly at the all-atom resolution where equations of motion are integrated with timesteps on the order of femtoseconds…

As molecular scientists have made progress in their ability to engineer nano-scale molecular structure, we are facing new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs…

Molecule- and particle-based simulations provide the tools to test, in microscopic detail, the validity of classical nucleation theory. In this endeavour, determining nucleation mechanisms and rates for phase separation requires an…

Materials Science · Physics 2023-02-27 Aaron R. Finney , Matteo Salvalaglio

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…

Recent advancements in protein docking site prediction have highlighted the limitations of traditional rigid docking algorithms, like PIPER, which often neglect critical stochastic elements such as solvent-induced fluctuations. These…

Quantitative Methods · Quantitative Biology 2024-12-02 Nanjie Chen , Dongliang Yu , Dmitri Beglov , Mark Kon , Julio Enrique Castrillon-Candas

An unsolved challenge in the development of antigen specific immunotherapies is determining the optimal antigens to target. Comprehension of antigen-MHC binding is paramount towards achieving this goal. Here, we present CASTELO, a combined…

Quantitative Methods · Quantitative Biology 2020-12-09 David Bell , Giacomo Domeniconi , Chih-Chieh Yang , Ruhong Zhou , Leili Zhang , Guojing Cong

Folding protein dynamics has been an area of high interest for quite some time, especially given the increased focus on the field of Biophysics. Because folding dynamics occur on such short time scales, empirical techniques developed for…

Soft Condensed Matter · Physics 2022-10-11 Rickie Xian

At the scale of the individual cell, protein production is a stochastic process with multiple time scales, combining quick and slow random steps with discontinuous and smooth variation. Hybrid stochastic processes, in particular…

Molecular Networks · Quantitative Biology 2019-05-02 Guilherme C. P. Innocentini , Fernando Antoneli , Arran Hodgkinson , Ovidiu Radulescu

The accurate identification of antiviral peptides (AVPs) is crucial for novel drug development. However, existing methods still have limitations in capturing complex sequence dependencies and distinguishing confusing samples with high…

Machine Learning · Computer Science 2026-01-19 Xinru Wen , Weizhong Lin , zi liu , Xuan Xiao

Rigid bodies, made of smaller composite beads, are commonly used to simulate anisotropic particles with molecular dynamics or Monte Carlo methods. To accurately represent the particle shape and to obtain smooth and realistic effective pair…

Soft Condensed Matter · Physics 2024-02-20 B. Rusen Argun , Yu Fu , Antonia Statt

Molecular dynamics (MD) simulations can model the interactions between macromolecules with high spatiotemporal resolution but at a high computational cost. By combining high-throughput MD with Markov state models (MSMs), it is now possible…

Chemical Physics · Physics 2018-06-13 Manuel Dibak , Mauricio J. del Razo , David De Sancho , Christof Schütte , Frank Noé

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

This paper investigates the optimization problem of an infinite stage discrete time Markov decision process (MDP) with a long-run average metric considering both mean and variance of rewards together. Such performance metric is important…

Optimization and Control · Mathematics 2020-08-11 Li Xia