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Recent developments in enhanced sampling methods showed that it is possible to reconstruct ligand unbinding pathways with spatial and temporal resolution inaccessible to experiments. Ideally, such techniques should provide an atomistic…

Biological Physics · Physics 2019-12-17 Jakub Rydzewski

Alchemical free energy calculations are widely used in predicting pKa, and binding free energy calculations in biomolecular systems. These calculations are carried out using either Free Energy Perturbation (FEP) or Thermodynamic Integration…

Soft Condensed Matter · Physics 2022-11-28 Shivani Verma , Nisanth N. Nair

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

Molecular communication (MC), a biologically inspired technology, enables applications in nanonetworks and the Internet of Everything (IoE), with great potential for intra-body systems such as drug delivery, health monitoring, and disease…

Signal Processing · Electrical Eng. & Systems 2025-05-30 Dilara Aktas , Ozgur B. Akan

The efficiency of statistical sampling in broad-histogram Monte Carlo simulations can be considerably improved by optimizing the simulated extended ensemble for fastest equilibration. Here we describe how a recently developed feedback…

Statistical Mechanics · Physics 2007-12-13 Stefan Wessel , Norbert Stoop , Emanuel Gull , Simon Trebst , Matthias Troyer

Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling…

Biomolecules · Quantitative Biology 2018-04-04 Ngo Min Toan , D. Thirumalai

A major challenge in electrochemistry is to decouple the reactive intermediates of a catalytic cycle to optimise their energies independently. During the oxygen evolution reaction (OER), such energy interdependence results from the need to…

The presence of erratic or unstable paths in standard kinetic Monte Carlo simulations significantly undermines the accurate simulation and sampling of transition pathways. While typically reliable methods, such as the Gillespie algorithm,…

Statistical Mechanics · Physics 2024-12-03 Elad Korngut , Ohad Vilk , Michael Assaf

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial…

Quantitative Methods · Quantitative Biology 2025-02-24 Zizhuo Zhang , Lijun Wu , Kaiyuan Gao , Jiangchao Yao , Tao Qin , Bo Han

Machine learning potentials (MLPs) trained on data from quantum-mechanics based first-principles methods can approach the accuracy of the reference method at a fraction of the computational cost. To facilitate efficient MLP-based molecular…

Materials Science · Physics 2021-08-17 Michael S. Chen , Tobias Morawietz , Hideki Mori , Thomas E. Markland , Nongnuch Artrith

Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of \emph{forward models} that relate measured SAXS intensities and structural features, and that are suitable to model either…

Biomolecules · Quantitative Biology 2022-07-26 Mattia Bernetti , Kathleen B. Hall , Giovanni Bussi

Atomically detailed simulations of RNA folding have proven very challenging in view of the difficulties of developing realistic force fields and the intrinsic computational complexity of sampling rare conformational transitions. To tackle…

Soft Condensed Matter · Physics 2022-05-26 Gianmarco Lazzeri , Cristian Micheletti , Samuela Pasquali , Pietro Faccioli

In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical…

Statistical Mechanics · Physics 2010-12-30 Ayori Mitsutake , Yoshiharu Mori , Yuko Okamoto

Reinforcement learning (RL) has been pivotal in enhancing the reasoning capabilities of large language models (LLMs), but it often suffers from limited exploration and entropy collapse, where models exploit a narrow set of solutions,…

Machine Learning · Computer Science 2025-10-20 Shijia Kang , Muhan Zhang

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

We present a new simulation scheme which allows an efficient sampling of reconfigurable supramolecular structures made of polymeric constructs functionalized by reactive binding sites. The algorithm is based on the configurational bias…

Soft Condensed Matter · Physics 2015-06-23 Robin De Gernier , Tine Curk , Galina V. Dubacheva , Ralf P. Richter , Bortolo M. Mognetti

We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with implicit solvent. The main novel feature of our approach is the use of pre-calculated statistical libraries of…

Biological Physics · Physics 2010-03-04 A. B. Mamonov , X. Zhang , D. M. Zuckerman

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

The unfolding of molecular complexes or biomolecules under the influence of external mechanical forces can routinely be simulated with atomistic resolution. To obtain a match of the characteristic time scales with those of experimental…

Soft Condensed Matter · Physics 2024-07-17 Marco Oestereich , Jürgen Gauss , Gregor Diezemann

Gradient-based Discrete Samplers (GDSs) are effective for sampling discrete energy landscapes. However, they often stagnate in complex, non-convex settings. To improve exploration, we introduce the Discrete Replica EXchangE Langevin…

Machine Learning · Computer Science 2025-05-21 Haoyang Zheng , Hengrong Du , Ruqi Zhang , Guang Lin
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