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High-content phenotypic screening, including high-content imaging (HCI), has gained popularity in the last few years for its ability to characterize novel therapeutics without prior knowledge of the protein target. When combined with deep…

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren

Shape-based virtual screening is widely employed in ligand-based drug design to search chemical libraries for molecules with similar 3D shapes yet novel 2D chemical structures compared to known ligands. 3D deep generative models have the…

Chemical Physics · Physics 2022-10-12 Keir Adams , Connor W. Coley

In this paper, we propose a deep evolutionary learning (DEL) process that integrates fragment-based deep generative model and multi-objective evolutionary computation for molecular design. Our approach enables (1) evolutionary operations in…

Neural and Evolutionary Computing · Computer Science 2021-02-02 Yifeng Li , Hsu Kiang Ooi , Alain Tchagang

Efficient design and discovery of target-driven molecules is a critical step in facilitating lead optimization in drug discovery. Current approaches to develop molecules for a target protein are intuition-driven, hampered by slow iterative…

Machine Learning · Computer Science 2022-05-24 Andrew D. McNaughton , Mridula S. Bontha , Carter R. Knutson , Jenna A. Pope , Neeraj Kumar

Deep generative models have achieved tremendous success in designing novel drug molecules in recent years. A new thread of works have shown the great potential in advancing the specificity and success rate of in silico drug design by…

Machine Learning · Computer Science 2025-07-14 Xingang Peng , Shitong Luo , Jiaqi Guan , Qi Xie , Jian Peng , Jianzhu Ma

The prediction of molecular properties is a crucial task in the field of material and drug discovery. The potential benefits of using deep learning techniques are reflected in the wealth of recent literature. Still, these techniques are…

Machine Learning · Computer Science 2023-09-06 Minghao Guo , Veronika Thost , Samuel W Song , Adithya Balachandran , Payel Das , Jie Chen , Wojciech Matusik

Diffusion models have emerged as powerful tools for molecular generation, particularly in the context of 3D molecular structures. Inspired by non-equilibrium statistical physics, these models can generate 3D molecular structures with…

Chemical Physics · Physics 2025-05-16 Amira Alakhdar , Barnabas Poczos , Newell Washburn

To generate drug molecules of desired properties with computational methods is the holy grail in pharmaceutical research. Here we describe an AI strategy, retro drug design, or RDD, to generate novel small molecule drugs from scratch to…

Biomolecules · Quantitative Biology 2021-05-12 Yuhong Wang , Sam Michael , Ruili Huang , Jinghua Zhao , Katlin Recabo , Danielle Bougie , Qiang Shu , Paul Shinn , Hongmao Sun

De novo molecular generation is an essential task for science discovery. Recently, fragment-based deep generative models have attracted much research attention due to their flexibility in generating novel molecules based on existing…

Machine Learning · Computer Science 2023-02-28 Zijie Geng , Shufang Xie , Yingce Xia , Lijun Wu , Tao Qin , Jie Wang , Yongdong Zhang , Feng Wu , Tie-Yan Liu

We introduce a scheme for molecular simulations, the Deep Potential Molecular Dynamics (DeePMD) method, based on a many-body potential and interatomic forces generated by a carefully crafted deep neural network trained with ab initio data.…

Computational Physics · Physics 2018-04-11 Linfeng Zhang , Jiequn Han , Han Wang , Roberto Car , Weinan E

Dual-target therapeutic strategies have become a compelling approach and attracted significant attention due to various benefits, such as their potential in overcoming drug resistance in cancer therapy. Considering the tremendous success…

Machine Learning · Computer Science 2024-11-27 Xiangxin Zhou , Jiaqi Guan , Yijia Zhang , Xingang Peng , Liang Wang , Jianzhu Ma

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising…

Machine Learning · Computer Science 2022-09-05 Gökçe Uludoğan , Elif Ozkirimli , Kutlu O. Ulgen , Nilgün Karalı , Arzucan Özgür

Generative models have demonstrated substantial promise in Natural Language Processing (NLP) and have found application in designing molecules, as seen in General Pretrained Transformer (GPT) models. In our efforts to develop such a tool…

Machine Learning · Computer Science 2023-11-27 Niklas Dobberstein , Astrid Maass , Jan Hamaekers

Recent reasoning-based large language models have shown strong performance on tasks with verifiable outcomes, but their use in de novo molecular generation remains limited by the lack of training environments where rewards can be computed…

Machine Learning · Computer Science 2026-05-12 Philippe Formont , Maxime Darrin , Ismail Ben Ayed , Pablo Piantanida

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour

Deep generative models have recently emerged as a promising de novo drug design method. In this respect, deep generative conditional variational autoencoder (CVAE) models are a powerful approach for generating novel molecules with desired…

Machine Learning · Computer Science 2023-08-21 Guang Jun Nicholas Ang , De Tao Irwin Chin , Bingquan Shen

State-of-the-art models for 3D molecular generation are based on significant inductive biases, SE(3), permutation equivariance to respect symmetry and graph message-passing networks to capture local chemistry, yet the generated molecules…

Machine Learning · Computer Science 2025-07-02 Carlos Vonessen , Charles Harris , Miruna Cretu , Pietro Liò

Advances in deep generative models shed light on de novo molecule generation with desired properties. However, molecule generation targeted for dual protein targets still faces formidable challenges including protein 3D structure data…