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Understanding the kinetics of drug-protein interactions is paramount for drug design, yet the field lacks large-scale, dynamic data to move beyond static structural analysis. Here, we present DD-03B, a massively scalable database providing…

计算物理 · 物理学 2026-04-09 Maodong Li , Dechin Chen , Zhijun Pan , Zhe Wang , Yi Isaac Yang

Studying the pathways of ligand-receptor binding is essential to understand the mechanism of target recognition by small molecules. The binding free energy and kinetics of protein-ligand complexes can be computed using molecular dynamics…

化学物理 · 物理学 2023-08-14 Dhiman Ray , Michele Parrinello

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

机器学习 · 计算机科学 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Despite significant progress in static protein structure collection and prediction, the dynamic behavior of proteins, one of their most vital characteristics, has been largely overlooked in prior research. This oversight can be attributed…

Large parallel gains in the development of both computational resources as well as sampling methods have now made it possible to simulate dissociation events in ligand-protein complexes with all--atom resolution. Such encouraging progress,…

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with…

生物大分子 · 定量生物学 2025-03-07 Xiangxin Zhou , Yi Xiao , Haowei Lin , Xinheng He , Jiaqi Guan , Yang Wang , Qiang Liu , Feng Zhou , Liang Wang , Jianzhu Ma

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because…

生物大分子 · 定量生物学 2024-09-04 Yaosen Min , Ye Wei , Peizhuo Wang , Xiaoting Wang , Han Li , Nian Wu , Stefan Bauer , Shuxin Zheng , Yu Shi , Yingheng Wang , Ji Wu , Dan Zhao , Jianyang Zeng

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…

化学物理 · 物理学 2025-09-04 Bin Feng , Jiying Zhang , Xinni Zhang , Zijing Liu , Yu Li

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

生物大分子 · 定量生物学 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

Recent advancements in protein structure determination are revolutionizing our understanding of proteins. Still, a significant gap remains in the availability of comprehensive datasets that focus on the dynamics of proteins, which are…

生物大分子 · 定量生物学 2024-12-04 Antonio Mirarchi , Toni Giorgino , Gianni De Fabritiis

In recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural…

生物大分子 · 定量生物学 2020-03-31 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

The interaction of multiple fluids through a heterogeneous pore space leads to complex pore-scale flow dynamics, such as intermittent pathway flow. The non-local nature of these dynamics, and the size of the 4D datasets acquired to capture…

地球物理 · 物理学 2024-09-24 Aman Raizada , Steffen Berg , Sally M. Benson , Hamdi A. Tchelepi , Catherine Spurin

Coarse-graining of fully atomistic molecular dynamics simulations is a long-standing goal in order to allow the description of processes occurring on biologically relevant timescales. For example, the prediction of pathways, rates and…

生物物理 · 物理学 2020-06-12 Steffen Wolf , Benjamin Lickert , Simon Bray , Gerhard Stock

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

生物大分子 · 定量生物学 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Generating diverse, all-atom conformational ensembles of dynamic proteins such as G-protein-coupled receptors (GPCRs) is critical for understanding their function, yet most generative models simplify atomic detail or ignore conformational…

生物大分子 · 定量生物学 2025-08-19 Aditya Sengar , Ali Hariri , Daniel Probst , Patrick Barth , Pierre Vandergheynst

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…

生物大分子 · 定量生物学 2020-10-13 Daria B. Kokha , Bernd Doser , Stefan Richter , Fabian Ormersbach , Xingyi Cheng , Rebecca C. Wade

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.…

生物大分子 · 定量生物学 2023-12-20 Jintao Zhu , Zhonghui Gu , Jianfeng Pei , Luhua Lai

The latest biological findings observe that the traditional motionless 'lock-and-key' theory is not generally applicable because the receptor and ligand are constantly moving. Nonetheless, remarkable changes in associated atomic sites and…

计算工程、金融与科学 · 计算机科学 2023-11-01 Fang Wu , Shuting Jin , Yinghui Jiang , Xurui Jin , Bowen Tang , Zhangming Niu , Xiangrong Liu , Qiang Zhang , Xiangxiang Zeng , Stan Z. Li

Drug development is a critical but notoriously resource- and time-consuming process. In this manuscript, we develop a novel generative artificial intelligence (genAI) method DiffSMol to facilitate drug development. DiffSmol generates 3D…

机器学习 · 计算机科学 2025-02-11 Ziqi Chen , Bo Peng , Tianhua Zhai , Daniel Adu-Ampratwum , Xia Ning

Drug combination therapy is a well-established strategy for disease treatment with better effectiveness and less safety degradation. However, identifying novel drug combinations through wet-lab experiments is resource intensive due to the…

机器学习 · 计算机科学 2023-01-18 Zhihang Hu , Qinze Yu , Yucheng Guo , Taifeng Wang , Irwin King , Xin Gao , Le Song , Yu Li
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