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Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well…

Quantitative Methods · Quantitative Biology 2019-01-24 Thomas Löhr , Carlo Camilloni , Massimiliano Bonomi , Michele Vendruscolo

A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin , Jose N. Onuchic

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

We present a new method that combines alchemical transformation with physical pathway to accurately and efficiently compute the absolute binding free energy of receptor-ligand complex. Currently, the double decoupling method (DDM) and the…

Biomolecules · Quantitative Biology 2018-08-29 Nanjie Deng , Lauren Wickstrom , Emilio Gallicchio

Protein dynamics play a crucial role in protein biological functions and properties, and their traditional study typically relies on time-consuming molecular dynamics (MD) simulations conducted in silico. Recent advances in generative…

Biomolecules · Quantitative Biology 2025-06-02 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Aurélie Lozano , Vijil Chenthamarakshan , Payel Das , Jian Tang

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

To address the large gap between time scales that can be easily reached by molecular simulations and those required to understand protein dynamics, we propose a rapid self-consistent approximation of the side chain free energy at every…

Biomolecules · Quantitative Biology 2017-09-15 John M. Jumper , Karl F. Freed , Tobin R. Sosnick

The urgency of the energy transition requires improving the performance and longevity of hydrogen technologies. AlphaPEM is a dynamic one-dimensional (1D) physics-based PEM fuel cell system simulator, programmed in Python and experimentally…

Systems and Control · Electrical Eng. & Systems 2026-01-28 Raphaël Gass , Zhongliang Li , Rachid Outbib , Samir Jemeï , Daniel Hissel

Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a…

Machine Learning · Computer Science 2017-03-31 Joseph Gomes , Bharath Ramsundar , Evan N. Feinberg , Vijay S. Pande

We compute absolute binding affinities for two ligands bound to the FKBP protein using non-equilibrium unbinding simulations. The methodology is straight-forward, requiring little or no modification to many modern molecular simulation…

Biological Physics · Physics 2008-11-24 F. Marty Ytreberg

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

The detection of vibrational excitations of individual molecules on surfaces by scanning tunneling spectroscopy does not obey strict selection rules but rather propensity rules. The experimental verification of these is challenging because…

FeFETs hold strong potential for advancing memory and logic technologies, but their inherent randomness arising from both operational cycling and fabrication variability poses significant challenges for accurate and reliable modeling.…

Machine Learning · Computer Science 2025-08-06 Tasnia Nobi Afee , Jack Hutchins , Md Mazharul Islam , Thomas Kampfe , Ahmedullah Aziz

In a recent technical critique of the free energy principle (FEP) due to Aguilera-Millidge-Tschantz-Buckley, it is argued that there are a number of instances where the FEP$\unicode{x2014}$as conventionally written, in terms of densities…

Statistical Mechanics · Physics 2022-06-02 Dalton A R Sakthivadivel

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…

Biomolecules · Quantitative Biology 2009-11-13 Gregg Lois , Jerzy Blawzdziewicz , Corey S. O'Hern

In structure-based drug discovery, virtual screening using conventional molecular docking methods can be performed rapidly but suffers from limitations in prediction accuracy. Recently, Boltz-2 was proposed, achieving extremely high…

Biomolecules · Quantitative Biology 2025-08-26 Kairi Furui , Masahito Ohue

The ability to reliably predict the structures and stabilities of a molecular crystal and its polymorphs without any prior experimental information would be an invaluable tool for a number of fields, with specific and immediate applications…

This work addresses the question of whether it is possible to define simple pair-wise interaction terms to approximate free energies of proteins or polymers. Rather than ask how reliable a potential of mean force is, one can ask how…

Soft Condensed Matter · Physics 2009-10-31 Dirk Reith , Thomas Huber , Florian Mueller-Plathe , Andrew E. Torda

Phaseless auxiliary-field quantum Monte Carlo (ph-AFQMC) has emerged as a promising electronic structure method for correlated electronic systems. However, the quality of its predictions depends critically on the choice of trial…

Chemical Physics · Physics 2026-05-06 Don Danilov , Brad Ganoe , Leon Otis , Zhi Gong , Zixiang Lu , James Shee

Molecular dynamics simulations using empirical force fields (EFFs) are crucial for gaining fundamental insights into atomic structure and long timescale dynamics of Au nanoclusters with far-reaching applications in energy and devices. This…

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