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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…

Biomolecules · Quantitative Biology 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

3D generative models have shown significant promise in structure-based drug design (SBDD), particularly in discovering ligands tailored to specific target binding sites. Existing algorithms often focus primarily on ligand-target binding,…

Deep generative models have been applied with increasing success to the generation of two dimensional molecules as SMILES strings and molecular graphs. In this work we describe for the first time a deep generative model that can generate 3D…

Chemical Physics · Physics 2020-11-24 Tomohide Masuda , Matthew Ragoza , David Ryan Koes

We devise an approach for targeted molecular design, a problem of interest in computational drug discovery: given a target protein site, we wish to generate a chemical with both high binding affinity to the target and satisfactory…

Artificial Intelligence · Computer Science 2018-09-07 Tristan Aumentado-Armstrong

Finding drug-like compounds with high bioactivity is essential for drug discovery, but the task is complicated by the high cost of chemical synthesis and validation. With their outstanding performance in de novo drug design, deep generative…

Quantitative Methods · Quantitative Biology 2023-01-03 Yibo Li , Jianfeng Pei , Luhua Lai

Molecular docking is a crucial step in drug development, which enables the virtual screening of compound libraries to identify potential ligands that target proteins of interest. However, the computational complexity of traditional docking…

Machine Learning · Computer Science 2024-12-06 Zhangfan Yang , Junkai Ji , Shan He , Jianqiang Li , Tiantian He , Ruibin Bai , Zexuan Zhu , Yew Soon Ong

Massive molecular simulations of drug-target proteins have been used as a tool to understand disease mechanism and develop therapeutics. This work focuses on learning a generative neural network on a structural ensemble of a drug-target…

Machine Learning · Computer Science 2022-05-24 N. Joseph Tatro , Payel Das , Pin-Yu Chen , Vijil Chenthamarakshan , Rongjie Lai

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…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Accurate prediction of protein-ligand binding structures, a task known as molecular docking is crucial for drug design but remains challenging. While deep learning has shown promise, existing methods often depend on holo-protein structures…

Biomolecules · Quantitative Biology 2024-02-22 Yufei Huang , Odin Zhang , Lirong Wu , Cheng Tan , Haitao Lin , Zhangyang Gao , Siyuan Li , Stan. Z. Li

We propose a framework based on Quadratic Unconstrained Binary Optimization (QUBO) for generating plausible ligand binding poses within protein pockets, enabling efficient structure-based virtual screening. The method discretizes the…

Biomolecules · Quantitative Biology 2025-07-29 Pei-Kun Yang

We report a 3D structure-based method of predicting protein-protein interaction partners. It involves screening for pairs of tetrahedra representing interacting amino acids at the interface of the protein-protein complex, with one…

Biomolecules · Quantitative Biology 2015-05-06 Vicente M. Reyes

Structure-based drug design (SBDD) is crucial for developing specific and effective therapeutics against protein targets but remains challenging due to complex protein-ligand interactions and vast chemical space. Although language models…

Biomolecules · Quantitative Biology 2024-08-20 Cong Fu , Xiner Li , Blake Olson , Heng Ji , Shuiwang Ji

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

The field of machine learning for drug discovery is witnessing an explosion of novel methods. These methods are often benchmarked on simple physicochemical properties such as solubility or general druglikeness, which can be readily…

Proteins play crucial roles in every cellular process by interacting with each other, with nucleic acids, metabolites, and other molecules. The resulting assemblies can be very large and intricate and pose challenges to experimental…

Biomolecules · Quantitative Biology 2021-03-16 Charlotte W. van Noort , Rodrigo V. Honorato , Alexandre M. J. J. Bonvin

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL)…

Machine Learning · Computer Science 2026-03-24 Alex Morehead , Nabin Giri , Jian Liu , Pawan Neupane , Jianlin Cheng

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…

Computational Physics · Physics 2026-04-09 Maodong Li , Dechin Chen , Zhijun Pan , Zhe Wang , Yi Isaac Yang

Molecular docking that predicts the bound structures of small molecules (ligands) to their protein targets, plays a vital role in drug discovery. However, existing docking methods often face limitations: they either overlook crucial…

Quantitative Methods · Quantitative Biology 2025-02-24 Zizhuo Zhang , Lijun Wu , Kaiyuan Gao , Jiangchao Yao , Tao Qin , Bo Han

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…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

AI-powered drug discovery typically relies on the successful prediction of compound-protein interactions, which are pivotal for the evaluation of designed compound molecules in structure-based drug design and represent a core challenge in…

Biomolecules · Quantitative Biology 2025-04-22 Pingfei Zhu , Chenyang Zhao , Haishi Zhao , Bo Yang