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Comprehending the long-timescale dynamics of protein-ligand complexes is very important for drug discovery and structural biology, but it continues to be computationally challenging for large biomolecular systems. We introduce…

Biomolecules · Quantitative Biology 2025-08-26 Rakesh Thakur , Riya Gupta

Mass spectrometry plays a fundamental role in elucidating the structures of unknown molecules and subsequent scientific discoveries. One formulation of the structure elucidation task is the conditional de novo generation of molecular…

Machine Learning · Computer Science 2025-05-29 Montgomery Bohde , Mrunali Manjrekar , Runzhong Wang , Shuiwang Ji , Connor W. Coley

Diffusion Transformers (DiTs) have demonstrated strong performance in generative modeling, particularly in image synthesis, making them a compelling choice for molecular conformer generation. However, applying DiTs to molecules introduces…

Machine Learning · Computer Science 2025-11-12 J. Thorben Frank , Winfried Ripken , Gregor Lied , Klaus-Robert Müller , Oliver T. Unke , Stefan Chmiela

Generating molecules that bind to specific protein targets via diffusion models has shown good promise for structure-based drug design and molecule optimization. Especially, the diffusion models with binding interaction guidance enables…

Machine Learning · Computer Science 2025-05-12 Anjie Qiao , Hao Zhang , Qianmu Yuan , Qirui Deng , Jingtian Su , Weifeng Huang , Huihao Zhou , Guo-Bo Li , Zhen Wang , Jinping Lei

Molecular 3D conformations play a key role in determining how molecules interact with other molecules or protein surfaces. Recent deep learning advancements have improved conformation prediction, but slow training speeds and difficulties in…

Machine Learning · Computer Science 2024-12-17 Qingwen Tian , Yuxin Xu , Yixuan Yang , Zhen Wang , Ziqi Liu , Pengju Yan , Xiaolin Li

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

In silico prediction of the ligand binding pose to a given protein target is a crucial but challenging task in drug discovery. This work focuses on blind flexible selfdocking, where we aim to predict the positions, orientations and…

Biomolecules · Quantitative Biology 2023-06-02 Yangtian Zhang , Huiyu Cai , Chence Shi , Bozitao Zhong , Jian Tang

Designing mechanical linkages to achieve target end-effector trajectories presents a fundamental challenge due to the intricate coupling between continuous node placements, discrete topological configurations, and nonlinear kinematic…

Machine Learning · Computer Science 2026-01-08 Yayati Jadhav , Amir Barati Farimani

Molecular optimization, aimed at improving binding affinity or other molecular properties, is a crucial task in drug discovery that often relies on the expertise of medicinal chemists. Recently, deep learning-based 3D generative models…

Machine Learning · Computer Science 2025-05-01 Anjie Qiao , Junjie Xie , Weifeng Huang , Hao Zhang , Jiahua Rao , Shuangjia Zheng , Yuedong Yang , Zhen Wang , Guo-Bo Li , Jinping Lei

Fragment-Based Drug Discovery (FBDD) is a popular approach in early drug development, but designing effective linkers to combine disconnected molecular fragments into chemically and pharmacologically viable candidates remains challenging.…

Machine Learning · Computer Science 2025-09-24 Xuefeng Liu , Songhao Jiang , Qinan Huang , Tinson Xu , Ian Foster , Mengdi Wang , Hening Lin , Rick Stevens

Generating visual layouts is an essential ingredient of graphic design. The ability to condition layout generation on a partial subset of component attributes is critical to real-world applications that involve user interaction. Recently,…

Computer Vision and Pattern Recognition · Computer Science 2023-03-08 Elad Levi , Eli Brosh , Mykola Mykhailych , Meir Perez

n this work, we propose a latent molecular diffusion model that can make the generated 3D molecules rich in diversity and maintain rich geometric features. The model captures the information of the forces and local constraints between atoms…

Machine Learning · Computer Science 2024-12-06 Xiang Chen

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering.…

Biomolecules · Quantitative Biology 2022-06-07 Hannes Stärk , Octavian-Eugen Ganea , Lagnajit Pattanaik , Regina Barzilay , Tommi Jaakkola

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

Molecular conformation generation plays key roles in computational drug design. Recently developed deep learning methods, particularly diffusion models have reached competitive performance over traditional cheminformatical approaches.…

Machine Learning · Computer Science 2025-01-10 Yixuan Yang , Xingyu Fang , Zhaowen Cheng , Pengju Yan , Xiaolin Li

Determining the binding pose of a ligand to a protein, known as molecular docking, is a fundamental task in drug discovery. Generative approaches promise faster, improved, and more diverse pose sampling than physics-based methods, but are…

Machine Learning · Computer Science 2026-03-26 Alvaro Prat , Leo Zhang , Charlotte M. Deane , Yee Whye Teh , Garrett M. Morris

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

Diffusion Probabilistic Models (DPMs) have demonstrated significant potential in 3D medical image segmentation tasks. However, their high computational cost and inability to fully capture global 3D contextual information limit their…

Image and Video Processing · Electrical Eng. & Systems 2025-04-17 Kangbo Ma

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Computational drug discovery strategies can be broadly placed in two categories: ligand-based methods which identify novel molecules by similarity with known ligands, and structure-based methods which predict molecules with high-affinity to…

Quantitative Methods · Quantitative Biology 2019-05-30 Vincent Mallet , Carlos G. Oliver , Nicolas Moitessier , Jerome Waldispuhl