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Related papers: Binding Free Energies without Alchemy

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The immersed boundary-finite element method (IBFE) is an approach to describing the dynamics of an elastic structure immersed in an incompressible viscous fluid. In this formulation, there are discontinuities in the pressure and viscous…

Numerical Analysis · Mathematics 2020-03-18 Charles Puelz , Boyce E. Griffith

The quality of astrochemical models is highly dependent on reliable binding energy (BE) values that consider the morphological and energetic variety of binding sites on the surface of ice-grain mantles. Here, we present the Binding Energy…

Instrumentation and Methods for Astrophysics · Physics 2022-08-31 Giulia M. Bovolenta , Stefan Vogt-Geisse , Stefano Bovino , Tommaso Grassi

We present convergence results for an adaptive algorithm to compute free energies, namely the adaptive biasing force (ABF) method. The free energy is the effective potential associated to a so-called reaction coordinate (RC). Computing free…

Analysis of PDEs · Mathematics 2010-05-20 Tony Lelievre , Kimiya Minoukadeh

We present an Adaptively Biased Molecular Dynamics (ABMD) method for the computation of the free energy surface of a reaction coordinate using non-equilibrium dynamics. The ABMD method belongs to the general category of umbrella sampling…

Materials Science · Physics 2008-04-16 Volodymyr Babin , Christopher Roland , Celeste Sagui

The unique electron deficiency of boron makes it challenging to determine the stable structures, leading to a wide variety of forms. In this work, we introduce a statistical model based on grand canonical ensemble theory that incorporates…

Materials Science · Physics 2025-02-11 Chang-Chun He , Shao-Gang Xu , Yu-Jun Zhao , Hu Xu , Xiao-Bao Yang

We apply the Alchemical Transfer Method (ATM) and a bespoke fixed partial charge force field to the SAMPL9 bCD host-guest binding free energy prediction challenge that comprises a combination of complexes formed between five phenothiazine…

Chemical Physics · Physics 2023-02-28 Sheenam Khuttan , Solmaz Azimi , Joe Z. Wu , Sebastian Dick , Chuanjie Wu , Huafeng Xu , Emilio Gallicchio

The development of machine-learning (ML) potentials offers significant accuracy improvements compared to molecular mechanics (MM) because of the inclusion of quantum-mechanical effects in molecular interactions. However, ML simulations are…

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity…

Development of scoring functions (SFs) used to predict protein-ligand binding energies requires high-quality 3D structures and binding assay data for training and testing their parameters. In this work, we show that one of the widely-used…

Biological Physics · Physics 2025-03-10 Yingze Wang , Kunyang Sun , Jie Li , Xingyi Guan , Oufan Zhang , Dorian Bagni , Teresa Head-Gordon

We describe a non-parametric approach for accurate determination of the slowest relaxation eigenvectors of molecular dynamics. The approach is blind as it uses no system specific information. In particular, it does not require a functional…

Chemical Physics · Physics 2021-03-04 Sergei Krivov

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Molecular docking, a key technique in structure-based drug design, plays pivotal roles in protein-ligand interaction modeling, hit identification and optimization, in which accurate prediction of protein-ligand binding mode is essential.…

Biomolecules · Quantitative Biology 2023-12-20 Jintao Zhu , Zhonghui Gu , Jianfeng Pei , Luhua Lai

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

Binding free energies are a key element in understanding and predicting the strength of protein--drug interactions. While classical free energy simulations yield good results for many purely organic ligands, drugs including transition metal…

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li

The assembly of proteins in membranes plays a key role in many crucial cellular pathways. Despite their importance, characterizing transmembrane assembly remains challenging for experiments and simulations. Equilibrium molecular dynamics…

Soft Condensed Matter · Physics 2024-08-05 Emil Jackel , Gianmarco Lazzeri , Roberto Covino

Specific binding of proteins to DNA is one of the most common ways in which gene expression is controlled. Although general rules for the DNA-protein recognition can be derived, the ambiguous and complex nature of this mechanism precludes a…

Biomolecules · Quantitative Biology 2007-12-17 E. Moroni , M. Caselle , F. Fogolari

Accurate estimation of mutational effects on protein-protein binding energies is an open problem with applications in structural biology and therapeutic design. Several deep learning predictors for this task have been proposed, but,…

Biomolecules · Quantitative Biology 2025-07-09 Arthur Deng , Karsten Householder , Fang Wu , Sebastian Thrun , K. Christopher Garcia , Brian Trippe

From the onset of fundamental statistical mechanical constructs formulated in the late 19th century, alchemical free-energy methods slowly emerged and transitioned to become operational tools of biomolecular simulation applicable to a wide…

Computational Physics · Physics 2025-10-31 Daniele Macuglia , Giovanni Ciccotti , Benoît Roux

Comparison of free energies between different phases and different compositions underlies the prediction of alloy phase diagrams. To allow direct comparison, consistent reference points for the energies or enthalpies are required, and the…

Materials Science · Physics 2021-05-19 Yang Huang , Michael Widom , Michael C. Gao