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Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

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

The concept of a protein diffusing in its free energy folding landscape has been fruitful for both theory and experiment. Yet the choice of the reaction coordinate (RC) introduces an undesirable degree of arbitrariness into the problem. We…

Biological Physics · Physics 2015-05-19 Michael Hinczewski , Yann von Hansen , Joachim Dzubiella , Roland R. Netz

Standard flavors of density-functional theory (DFT) calculations are known to fail in describing anions, due to large self-interaction errors. The problem may be circumvented by using localized basis sets of reduced size, leaving no…

Chemical Physics · Physics 2019-12-23 Francesco Nattino , Céline Dupont , Nicola Marzari , Oliviero Andreussi

We calculated the docking energies between plumbagin and cyclodextrins, using density functional theory (DFT) with several functionals and some semi-empirical methods. Our DFT results revealed that GD3 dispersion force correction…

Rapid and accurate assessment of protein structural models is essential for protein structure prediction and design. Great progress has been made in this regard, especially by recent development of ``knowledge-based'' potentials. Various…

Computational Physics · Physics 2019-07-12 Shiyang Long , Pu Tian

Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were…

Biomolecules · Quantitative Biology 2020-12-29 Ameya Harmalkar , Jeffrey J. Gray

Predicting the docking between proteins and ligands is a crucial and challenging task for drug discovery. However, traditional docking methods mainly rely on scoring functions, and deep learning-based docking approaches usually neglect the…

Biomolecules · Quantitative Biology 2026-01-06 Yiqiang Yi , Xu Wan , Yatao Bian , Le Ou-Yang , Peilin Zhao

An effective potential function is critical for protein structure prediction and folding simulation. Simplified protein models such as those requiring only $C_\alpha$ or backbone atoms are attractive because they enable efficient search of…

Biomolecules · Quantitative Biology 2007-05-23 Jinfeng Zhang , Rong Chen , Jie Liang

Powerful generative AI models of protein-ligand structure have recently been proposed, but few of these methods support both flexible protein-ligand docking and affinity estimation. Of those that do, none can directly model multiple binding…

Machine Learning · Computer Science 2025-03-25 Alex Morehead , Jianlin Cheng

Predicting interactions between biomolecules, such as protein-protein complexes, remains a challenging problem. Despite the many advancements done so far, the performances of docking protocols are deeply dependent on their capability of…

Biomolecules · Quantitative Biology 2025-08-19 Greta Grassmann , Lorenzo Di Rienzo , Giancarlo Ruocco , Mattia Miotto , Edoardo Milanetti

A goal of computational studies of protein-protein interfaces (PPIs) is to predict the binding site between two monomers that form a heterodimer. The simplest version of this problem is to rigidly re-dock the bound forms of the monomers,…

Biomolecules · Quantitative Biology 2026-01-08 Jacob Sumner , Grace Meng , Naomi Brandt , Alex T. Grigas , Andrés Córdoba , Mark D. Shattuck , Corey S. O'Hern

Predicting changes in binding free energy ($\Delta\Delta G$) is a vital task in protein engineering and protein-protein interaction (PPI) engineering for drug discovery. Previous works have observed a high correlation between $\Delta\Delta…

Machine Learning · Computer Science 2025-08-15 Patrick Soga , Zhenyu Lei , Yinhan He , Camille Bilodeau , Jundong Li

The penetration of distributed renewable energy (DRE) greatly raises the risk of distribution network operation such as peak shaving and voltage stability. Battery energy storage (BES) has been widely accepted as the most potential…

Optimization and Control · Mathematics 2017-07-03 Chenghui Tang , Jian Xu , Yuanzhang Sun , Siyang Liao , Deping Ke , Xiong Li

Optimal structure of proteins is described by linear stochastic differential equation with mean decrease of free energy and volatility. Structure determining strategy is given by a twin of stochastic variables for which empirical conditions…

Biomolecules · Quantitative Biology 2007-05-23 Toshio Fukumi

The diffusion learning method, DiffDock, for docking small-molecule ligands into protein binding sites was recently introduced. Results included comparisons to more conventional docking approaches, with DiffDock showing superior…

Artificial Intelligence · Computer Science 2024-12-10 Ajay N. Jain , Ann E. Cleves , W. Patrick Walters

We introduce an energy functional for ground-state electronic structure calculations. Its variables are the natural spin-orbitals of singlet many-body wave functions and their joint occupation probabilities deriving from controlled…

Chemical Physics · Physics 2016-12-04 Ralph Gebauer , Morrel H. Cohen , Roberto Car

In this paper we present the parameterization of a new interionic potential for stoichiometric, reduced and doped CeO$_2$. We use a dipole-polarizable potential (DIPPIM) and optimize its parameters by fitting them to a series of DFT…

Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve description of IDPs/IDRs, but are largely in disagreement with solution…

Protein-protein interactions (PPIs) govern nearly all cellular processes, yet computational methods for identifying binding partners typically produce ranked predictions without mechanistic justification. This creates a fundamental barrier…

Quantitative Methods · Quantitative Biology 2026-05-22 Kingsley Yeon , Xuefeng Liu , Promit Ghosal