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Structure-based drug design (SBDD) aims to efficiently discover high-affinity ligands within vast chemical spaces. However, current generative models struggle with objective misalignment and rigid sampling budgets. We present MolFORM, a…

Computational Engineering, Finance, and Science · Computer Science 2026-02-26 Daiheng Zhang , Zhao Zhang

Machine learning methods have been used to accelerate the molecule optimization process. However, efficient search for optimized molecules satisfying several properties with scarce labeled data remains a challenge for machine learning…

Biomolecules · Quantitative Biology 2022-12-20 Xin Xia , Yansen Su , Chunhou Zheng , Xiangxiang Zeng

Molecular optimization, which aims to discover improved molecules from a vast chemical search space, is a critical step in chemical development. Various artificial intelligence technologies have demonstrated high effectiveness and…

Chemical Physics · Physics 2024-11-26 Xin Xia , Yajie Zhang , Xiangxiang Zeng , Xingyi Zhang , Chunhou Zheng , Yansen Su

The rapid discovery of new chemical compounds is essential for advancing global health and developing treatments. While generative models show promise in creating novel molecules, challenges remain in ensuring the real-world applicability…

Biomolecules · Quantitative Biology 2025-09-29 Onur Boyar , Hiroyuki Hanada , Ichiro Takeuchi

Molecular optimization is a key challenge in drug discovery and material science domain, involving the design of molecules with desired properties. Existing methods focus predominantly on single-property optimization, necessitating…

Machine Learning · Computer Science 2024-09-13 Aye Phyu Phyu Aung , Jay Chaudhary , Ji Wei Yoon , Senthilnath Jayavelu

Multi-objective optimization (MOO) aims to optimize multiple, possibly conflicting objectives with widespread applications. We introduce a novel interacting particle method for MOO inspired by molecular dynamics simulations. Our approach…

Machine Learning · Computer Science 2024-11-22 Yinuo Ren , Tesi Xiao , Tanmay Gangwani , Anshuka Rangi , Holakou Rahmanian , Lexing Ying , Subhajit Sanyal

Machine learning based methods have shown potential for optimizing existing molecules with more desirable properties, a critical step towards accelerating new chemical discovery. Here we propose QMO, a generic query-based molecule…

Machine Learning · Computer Science 2022-04-21 Samuel Hoffman , Vijil Chenthamarakshan , Kahini Wadhawan , Pin-Yu Chen , Payel Das

Molecule optimization is a fundamental task for accelerating drug discovery, with the goal of generating new valid molecules that maximize multiple drug properties while maintaining similarity to the input molecule. Existing generative…

Machine Learning · Computer Science 2024-07-02 Tianfan Fu , Cao Xiao , Xinhao Li , Lucas M. Glass , Jimeng Sun

Efficient optimization of molecules with targeted properties remains a significant challenge due to the vast size and discrete nature of chemical compound space. Conventional machine-learning-based optimization approaches typically require…

Chemical Physics · Physics 2026-03-04 Yun-Wen Mao , Roman V. Krems

Recent advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD)…

Machine Learning · Computer Science 2025-07-29 Yi He , Ailun Wang , Zhi Wang , Yu Liu , Xingyuan Xu , Wen Yan

The integration of deep learning, particularly AI-Generated Content, with high-quality data derived from ab initio calculations has emerged as a promising avenue for transforming the landscape of scientific research. However, the challenge…

Machine Learning · Computer Science 2024-12-11 Kaiwei Zhang , Yange Lin , Guangcheng Wu , Yuxiang Ren , Xuecang Zhang , Bo wang , Xiaoyu Zhang , Weitao Du

Structure-based drug design (SBDD), which maps target proteins to candidate molecular ligands, is a fundamental task in drug discovery. Effectively aligning protein structural representations with molecular representations, and ensuring…

Artificial Intelligence · Computer Science 2025-11-03 Wei Zhang , Zekun Guo , Yingce Xia , Peiran Jin , Shufang Xie , Tao Qin , Xiang-Yang Li

Multi-objective optimization (MOO) lies at the core of many machine learning (ML) applications that involve multiple, potentially conflicting objectives (e.g., multi-task learning, multi-objective reinforcement learning, among many others).…

Machine Learning · Computer Science 2024-12-18 Mingjing Xu , Peizhong Ju , Jia Liu , Haibo Yang

The development of artificial intelligence (AI) for science has led to the emergence of learning-based research paradigms, necessitating a compelling reevaluation of the design of multi-objective optimization (MOO) methods. The new…

Machine Learning · Computer Science 2023-11-02 Linxi Yang , Xinmin Yang , Liping Tang

The structural design of functional molecules, also called molecular optimization, is an essential chemical science and engineering task with important applications, such as drug discovery. Deep generative models and combinatorial…

Machine Learning · Computer Science 2022-01-25 Tianfan Fu , Wenhao Gao , Cao Xiao , Jacob Yasonik , Connor W. Coley , Jimeng Sun

Molecule optimization is about generating molecule $Y$ with more desirable properties based on an input molecule $X$. The state-of-the-art approaches partition the molecules into a large set of substructures $S$ and grow the new molecule…

Machine Learning · Computer Science 2019-12-13 Tianfan Fu , Cao Xiao , Jimeng Sun

Nonlinear conjugate gradient methods have recently garnered significant attention within the multiobjective optimization community. These methods aim to maintain consistency in conjugate parameters with their single-objective optimization…

Optimization and Control · Mathematics 2024-05-15 Jian Chen , Liping Tang. Xinmin Yang

Stochastic First-Order (SFO) methods have been a cornerstone in addressing a broad spectrum of modern machine learning (ML) challenges. However, their efficacy is increasingly questioned, especially in large-scale applications where…

Machine Learning · Computer Science 2024-08-01 Di Zhang , Suvrajeet Sen

Molecule optimization is a critical step in drug development to improve desired properties of drug candidates through chemical modification. We developed a novel deep generative model Modof over molecular graphs for molecule optimization.…

Machine Learning · Computer Science 2022-01-17 Ziqi Chen , Martin Renqiang Min , Srinivasan Parthasarathy , Xia Ning

Molecular optimization in drug discovery aims to discover molecules with improved target properties, but practical lead optimization often requires more than high predicted scores. A useful candidate should also be actionable: it should be…

Machine Learning · Computer Science 2026-05-12 Yang Qiao , Bo Pan , Hao-Wei Pang , Peter Zhiping Zhang , Liying Zhang , Liang Zhao
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