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Molecular dynamics (MD) simulations are essential tools in computational chemistry and drug discovery, offering crucial insights into dynamic molecular behavior. However, their utility is significantly limited by substantial computational…

Chemical Physics · Physics 2025-09-04 Bin Feng , Jiying Zhang , Xinni Zhang , Zijing Liu , Yu Li

Interacting-Particle Reaction Dynamics (iPRD) simulates the spatiotemporal evolution of particles that experience interaction forces and can react with one another. The combination of interaction forces and reactions enable a wide range of…

Chemical Physics · Physics 2018-07-20 Christoph Fröhner , Frank Noé

Docking-based virtual screening (VS process) selects ligands with potential pharmacological activities from millions of molecules using computational docking methods, which greatly could reduce the number of compounds for experimental…

Quantitative Methods · Quantitative Biology 2021-10-26 Wei Ma , Qin Xie , Jianhang Zhang , Shiliang Li , Youjun Xu , Xiaobing Deng , Weilin Zhang

Protein-ligand interactions are one of the fundamental types of molecular interactions in living systems. Ligands are small molecules that interact with protein molecules at specific regions on their surfaces called binding sites. Tasks…

Biomolecules · Quantitative Biology 2020-08-11 Arnab Bhadra , Kalidas Y

Peripheral membrane proteins can reversibly and specifically bind to biological membranes to carry out functions such as cell signalling, enzymatic activity, or membrane remodelling. Structures of these proteins and of their lipid-binding…

Biological Physics · Physics 2023-11-14 Andreas Haahr Larsen , Laura H. John , Mark S. P. Sansom , Robin A. Corey

We have earlier reported the iMOLSDOCK technique to perform induced-fit peptide-protein docking. iMOLSDOCK uses the mutually orthogonal Latin squares (MOLS) technique to sample the conformation and the docking pose of the small molecule…

Biological Physics · Physics 2020-10-13 D. Sam Paul , N. Gautham

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

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

Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation.…

Biomolecules · Quantitative Biology 2025-01-28 Jiaqi Guan , Jiahan Li , Xiangxin Zhou , Xingang Peng , Sheng Wang , Yunan Luo , Jian Peng , Jianzhu Ma

Prediction of protein-ligand binding affinity is a major goal in drug discovery. Generally, free energy gap is calculated between two states (e.g., ligand binding and unbinding). The energy gap implicitly includes the effects of changes in…

Biomolecules · Quantitative Biology 2022-05-20 Ikki Yasuda , Katsuhiro Endo , Eiji Yamamoto , Yoshinori Hirano , Kenji Yasuoka

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary…

Machine Learning · Computer Science 2026-05-26 Zhaohan Meng , Zhen Bai , Ke Yuan , Iadh Ounis , Zaiqiao Meng , Hao Xu , Joseph Loscalzo

We introduce mapping-variable ring polymer molecular dynamics (MV-RPMD), a model dynamics for the direct simulation of multi-electron processes. An extension of the RPMD idea, this method is based on an exact, imaginary time path-integral…

Statistical Mechanics · Physics 2015-06-17 Nandini Ananth

Interaction in virtual reality (VR) environments is essential to achieve a pleasant and immersive experience. Most of the currently existing VR applications, lack of robust object grasping and manipulation, which are the cornerstone of…

Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly…

Physics Education · Physics 2015-02-27 Daniel V. Schroeder

We here report on non-equilibrium targeted Molecular Dynamics simulations as tool for the estimation of protein-ligand unbinding kinetics. Correlating simulations with experimental data from SPR kinetics measurements and X-ray…

The dissociation of ligands from proteins and other biomacromolecules occurs over a wide range of timescales. For most pharmaceutically relevant inhibitors, these timescales are far beyond those that are accessible by conventional molecular…

Biomolecules · Quantitative Biology 2020-10-13 Daria B. Kokha , Bernd Doser , Stefan Richter , Fabian Ormersbach , Xingyi Cheng , Rebecca C. Wade

Whilst the primary bottleneck to a number of computational workflows was not so long ago limited by processing power, the rise of machine learning technologies has resulted in a paradigm shift which places increasing value on issues related…

This study introduces a novel computational approach based on ratchet-and-pawl molecular dynamics (rMD) for accurately estimating ligand dissociation kinetics in protein-ligand complexes. By integrating Kramers' theory with Bell's equation,…

Chemical Physics · Physics 2025-08-19 Bruno Stegani , Riccardo Capelli

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor…

Biomolecules · Quantitative Biology 2023-11-29 Shikun Feng , Minghao Li , Yinjun Jia , Weiying Ma , Yanyan Lan

Predicting the physical interaction of proteins is a cornerstone problem in computational biology. New classes of learning-based algorithms are actively being developed, and are typically trained end-to-end on protein complex structures…

Biomolecules · Quantitative Biology 2022-12-08 Siddharth Bhadra-Lobo , Georgy Derevyanko , Guillaume Lamoureux