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Related papers: Binding Free Energies without Alchemy

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Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and…

Chemical Physics · Physics 2025-12-09 Farzad Molani , Art E. Cho

Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force (BPMF) - the binding free energy between a flexible ligand and a rigid receptor - for a small organic ligand and a biological…

Chemical Physics · Physics 2020-06-30 David D. L Minh

In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction…

Chemical Physics · Physics 2025-06-27 Milana Bazayeva , Zhen Li , Danil Kaliakin , Fangchun Liang , Akhil Shajan , Susanta Das , Kenneth M. Merz

Learning binary representation is essential to large-scale computer vision tasks. Most existing algorithms require a separate quantization constraint to learn effective hashing functions. In this work, we present Direct Binary Embedding…

Computer Vision and Pattern Recognition · Computer Science 2017-06-06 Liu Liu , Alireza Rahimpour , Ali Taalimi , Hairong Qi

The principles behind the computation of protein-ligand binding free energies by Monte Carlo integration are described in detail. The simulation provides gas-phase binding free energies that can be converted to aqueous energies by solvation…

Chemical Physics · Physics 2017-01-25 Matthew Clark , Jeffrey S. Wiseman

Ab initio molecular dynamics (AIMD) simulations employing density functional theory (DFT) and plane waves are routinely carried out using density functionals at the level of Generalized Gradient Approximation (GGA). AIMD simulations…

Chemical Physics · Physics 2020-03-04 Sagarmoy Mandal , Nisanth N. Nair

The solvation free energy (SFE) of molecules and ions is a fundamental property governing their solvation behavior and solubility. Molecular simulations offer a route to compute SFEs using alchemical free energy methods, such as…

Chemical Physics · Physics 2026-04-21 Junting Yu , Shuo-Hui Li , Ding Pan

The molecular distributions obtained from canonical Monte Carlo simulations can be used to find an approximate interaction energy. This serves as the basis of a method for estimating the binding free energy for a ligand to a protein which…

Chemical Physics · Physics 2007-05-23 Charles F. F. Karney , Jason E. Ferrara , Clay D. Spence

Accurate prediction and optimization of protein-protein binding affinity is crucial for therapeutic antibody development. Although machine learning-based prediction methods $\Delta\Delta G$ are suitable for large-scale mutant screening,…

Biomolecules · Quantitative Biology 2024-09-19 Kairi Furui , Masahito Ohue

Alchemical free energy calculations via molecular dynamics have been widely used to obtain thermodynamic properties related to protein-ligand binding and solute-solvent interactions. Although soft-core modeling is the most common approach,…

Computational Physics · Physics 2023-01-03 Gabriela B. Correa , Jessica C. S. L. Maciel , Frederico W. Tavares , Charlles R. A. Abreu

We derive unconditionally stable and convergent variable-step BDF2 scheme for solving the MBE model with slope selection. The discrete orthogonal convolution kernels of the variable-step BDF2 method is commonly utilized recently for solving…

Numerical Analysis · Mathematics 2023-02-07 Xuan Zhao , Haifeng Zhang , Hong Sun

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

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…

Chemical Physics · Physics 2026-02-11 J. Harry Moore , Daniel J. Cole , Gabor Csanyi

Understanding design principles of biomolecular recognition is a key question of molecular biology. Yet the enormous complexity and diversity of biological molecules hamper the efforts to gain a predictive ability for the free energy of…

Biomolecules · Quantitative Biology 2012-04-19 Michael Elkin , Ingemar Andre , David B. Lukatsky

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

We present an implementation of alchemical free energy simulations at the quantum mechanical level by directly interpolating the electronic Hamiltonian. The method is compatible with any level of electronic structure theory and requires…

Chemical Physics · Physics 2024-09-02 Chenghan Li , Xing Zhang , Garnet Kin-Lic Chan

We propose a new model-free feature screening method based on energy distances for ultrahigh-dimensional binary classification problems. With a high probability, the proposed method retains only relevant features after discarding all the…

Methodology · Statistics 2023-05-19 Sarbojit Roy , Soham Sarkar , Subhajit Dutta , Anil K. Ghosh

Fluid-solid interfacial free energy (IFE) is a fundamental parameter influencing wetting behaviors, which play a crucial role across a broad range of industrial applications. Obtaining reliable data for fluid-solid IFE remains challenging…

Chemical Physics · Physics 2024-11-18 Yafan Yang , Arun Kumar Narayanan Nair , Shuyu Sun , Denvid Lau

We propose a method to compute free-energy differences from nonadiabatic alchemical transformations using flow-based generative models. The method, nonadiabatic force matching, hinges on estimating the dissipation along an alchemical…

Chemical Physics · Physics 2025-11-21 Jorge L. Rosa-Raíces , David T. Limmer

We present our blind predictions for the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL), 9th challenge, focusing on binding of WP6 (carboxy-pillar[6]arene) with ammonium/diammonium cationic guests. Host-guest binding…

Chemical Physics · Physics 2022-05-11 Piero Procacci , Guido Guarnieri