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The absolute free energy -- or partition function, equivalently -- of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule…

Biological Physics · Physics 2009-01-31 Xin Zhang , Artem B. Mamonov , Daniel M. Zuckerman

We propose an algorithm to obtain numerically approximate solutions of the direct Ising problem, that is, to compute the free energy and the equilibrium observables of spin systems with arbitrary two-spin interactions. To this purpose we…

Statistical Mechanics · Physics 2019-11-20 Simona Cocco , Giancarlo Croce , Francesco Zamponi

One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Daniel M. Zuckerman

This paper introduces a method for computing the Helmholtz free energy using the flow matching technique. Unlike previous work that utilized flow-based models for variational free energy calculations, this method provides bounds for free…

Computational Physics · Physics 2025-01-03 Lu Zhao , Lei Wang

We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Robert H. Swendsen , Daniel M. Zuckerman

Learning to sample from intractable distributions over discrete sets without relying on corresponding training data is a central problem in a wide range of fields, including Combinatorial Optimization. Currently, popular deep learning-based…

Machine Learning · Computer Science 2025-08-25 Sebastian Sanokowski , Sepp Hochreiter , Sebastian Lehner

We show how thermodynamic properties of molecular models can be computed over a large, multidimensional parameter space by combining multistate reweighting analysis with a linear basis function approach. This approach reduces the…

Chemical Physics · Physics 2016-05-18 Levi N. Naden , Michael R. Shirts

Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…

Chemical Physics · Physics 2016-09-28 Asaf Farhi , Bipin Singh

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus…

Statistical Mechanics · Physics 2007-10-04 F. Marini , C. Camilloni , D. Provasi , R. A. Broglia , G. Tiana

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

Calculating free energy differences is a topic of substantial interest and has many applications including molecular docking and hydration, solvation, and binding free energies which is used in computational drug discovery. However, in…

Chemical Physics · Physics 2013-10-16 Asaf Farhi

Free energy profiles serve as a fundamental bridge between microscopic atomic fluctuations and macroscopic thermodynamic observables. Estimating the free energy profile along a reaction coordinate, referred to as the potential of mean force…

The calculation of potential energy surfaces for quantum dynamics can be a time consuming task -- especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm…

Chemical Physics · Physics 2016-08-24 Markus Kowalewski , Elisabeth Larsson , Alfa Heryudono

We apply well-established concepts of Langevin sampling to derive a new class of algorithms for the efficient computation of free energy differences of fluctuating particles embedded in a 'fast' membrane, i.e., a membrane that…

Numerical Analysis · Mathematics 2020-10-01 Tobias Kies , Carsten Gräser , Luigi Delle Site , Ralf Kornhuber

We have developed a new simulation algorithm for free-energy calculations. The method is a multidimensional extension of the replica-exchange method. While pairs of replicas with different temperatures are exchanged during the simulation in…

Statistical Mechanics · Physics 2009-10-31 Yuji Sugita , Akio Kitao , Yuko Okamoto

Application of Jarzynski nonequilibrium work relation to free energy calculation is limited by the very slow convergence of the estimate when dissipation is high. We present a novel perturbation protocol able to improve the convergence of…

Statistical Mechanics · Physics 2008-01-03 Ognjen Perisic , Hui Lu

We study mean-field variational inference in a Bayesian linear model when the sample size n is comparable to the dimension p. In high dimensions, the common approach of minimizing a Kullback-Leibler divergence from the posterior…

Statistics Theory · Mathematics 2023-11-16 Michael Celentano , Zhou Fan , Licong Lin , Song Mei

We introduce an efficient and robust method to compute alchemical free energy differences, resulting from the application of multiple walker Adaptive Biasing Force (ABF) in conjunction with strongly damped Langevin $\lambda$-dynamics.…

A simple, efficient, and accurate method is proposed to map multi-dimensional free energy landscapes. The method combines the temperature-accelerated molecular dynamics (TAMD) proposed in [Maragliano & Vanden-Eijnden, Chem. Phys. Lett. 426,…

Computational Physics · Physics 2009-11-13 Luca Maragliano , Eric Vanden-Eijnden

We propose and analyze a class of adaptive sampling algorithms for multimodal distributions on a bounded domain, which share a structural resemblance to the classic overdamped Langevin dynamics. We first demonstrate that this class of…

Machine Learning · Computer Science 2024-11-26 Björn Engquist , Kui Ren , Yunan Yang