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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

We review uses of the generalized-ensemble algorithms for free-energy calculations in protein folding. Two of the well-known methods are multicanonical algorithm and replica-exchange method; the latter is also referred to as parallel…

Statistical Mechanics · Physics 2007-05-23 Y. Sugita , Y. Okamoto

Sampling Boltzmann probability distributions plays a key role in machine learning and optimization, motivating the design of hardware accelerators such as Ising machines. While the Ising model can in principle encode arbitrary optimization…

Machine Learning · Computer Science 2025-08-01 Corentin Delacour , M Mahmudul Hasan Sajeeb , Joao P. Hespanha , Kerem Y. Camsari

Engineering the free-energy surfaces (FES) of proteins and peptides is central to controlling conformational ensembles and their responses to perturbations. However, predicting how chemical modifications such as point mutations reshape the…

Biological Physics · Physics 2026-03-10 Muralika Medaparambath , Alexander Zhilkin , Dan Mendels

We describe a method that focuses sampling effort on a user-defined selection of a large system, which can lead to substantial decreases in computational effort by speeding up the calculation of nonbonded interactions. A naive approach can…

Statistical Mechanics · Physics 2023-08-28 Joshua Fass , Forrest York , Matthew Wittmann , Joseph Kaus , Yutong Zhao

We present a method for determining the free energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting…

Statistical Mechanics · Physics 2008-03-31 Alessandro Barducci , Giovanni Bussi , Michele Parrinello

When studying high-dimensional dynamical systems such as macromolecules, quantum systems and polymers, a prime concern is the identification of the most probable states and their stationary probabilities or free energies. Often, these…

Data Analysis, Statistics and Probability · Physics 2013-01-01 Hao Wu , Frank Noé

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

Sampling from high-dimensional distributions is a fundamental problem in statistical research and practice. However, great challenges emerge when the target density function is unnormalized and contains isolated modes. We tackle this…

Methodology · Statistics 2023-04-11 Yixuan Qiu , Xiao Wang

The bottleneck in enhanced sampling lies in finding collective variables (CVs) that can effectively accelerate protein conformational changes. True reaction coordinates (tRCs) that can predict the committor are considered the optimal CVs,…

Chemical Physics · Physics 2024-12-06 Huiyu Li , Ao Ma

With the rising number of machine learning competitions, the world has witnessed an exciting race for the best algorithms. However, the involved data selection process may fundamentally suffer from evidence ambiguity and concept drift…

Machine Learning · Computer Science 2020-06-15 Hoang D. Nguyen , Xuan-Son Vu , Quoc-Tuan Truong , Duc-Trong Le

Nested sampling (NS) has emerged as a powerful tool for exploring thermodynamic properties in materials science. However, its efficiency is often hindered by the limitations of Markov chain Monte Carlo (MCMC) sampling. In strongly…

Statistical Mechanics · Physics 2025-07-31 Nico Unglert , Livia Bartók Pártay , Georg K. H. Madsen

We propose a new multi-scale molecular dynamics simulation method which can achieve high accuracy and high sampling efficiency simultaneously without aforehand knowledge of the coarse grained (CG) potential and test it for a biomolecular…

Biological Physics · Physics 2009-08-05 Wenfei Li , Shoji Takada

Many biological processes occur on time scales longer than those accessible to molecular dynamics simulations. Identifying collective variables (CVs) and introducing an external potential to accelerate them is a popular approach to address…

Computational Physics · Physics 2024-10-24 Enrico Trizio , Andrea Rizzi , Pablo M. Piaggi , Michele Invernizzi , Luigi Bonati

We propose a new method for the determination of the weight factor for the simulated tempering method. In this method a short replica-exchange simulation is performed and the simulated tempering weight factor is obtained by the…

Statistical Mechanics · Physics 2009-10-31 A. Mitsutake , Y. Okamoto

In a resource-constrained Wireless Sensor Networks (WSNs), the optimization of the sampling and the transmission rates of each individual node is a crucial issue. A high volume of redundant data transmitted through the network will result…

Networking and Internet Architecture · Computer Science 2019-04-16 Gaby Bou Tayeh , Abdallah Makhoul , Charith Perera , Jacques Demerjian

Generalized ensemble methods such as Hamiltonian replica exchange (HREX) and expanded ensemble (EE) have been shown effective in free energy calculations for various contexts, given their ability to circumvent free energy barriers via…

Statistical Mechanics · Physics 2024-04-12 Wei-Tse Hsu , Michael R. Shirts

We propose the powerful integration of the Hybrid Monte Carlo (hybridMC) algorithm and Well-Tempered Metadynamics. This new algorithm, hybridMC-MetaD, enhances the flexibility and applicability of metadynamics by allowing for the…

Materials Science · Physics 2025-08-25 Charlotte Shiqi Zhao , Sun-Ting Tsai , Sharon C. Glotzer

Temperature-accelerated sliced sampling (TASS) is a well-established enhanced sampling method that facilitates exhaustive exploration of high-dimensional collective variable (CV) space through directed sampling employing a combination of…

Chemical Physics · Physics 2025-09-08 Sameer Saurav , Debjit Das , Ramsha Javed , Nisanth N. Nair

We introduce an extension to the Weighted Ensemble (WE) path sampling method to restrict sampling to a one dimensional path through a high dimensional phase space. Our method, which is based on the finite-temperature string method, permits…

Statistical Mechanics · Physics 2013-01-25 Joshua L. Adelman , Michael Grabe