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Probabilistic programming systems enable users to encode model structure and naturally reason about uncertainties, which can be leveraged towards improved Bayesian optimization (BO) methods. Here we present a probabilistic program embedding…

Artificial Intelligence · Computer Science 2019-02-06 Alexander Lavin

Combinatorial optimization algorithm is essential in computer-aided drug design by progressively exploring chemical space to design lead compounds with high affinity to target protein. However current methods face inherent challenges in…

Biomolecules · Quantitative Biology 2025-07-23 Hao Tuo , Yan Li , Xuanning Hu , Haishi Zhao , Xueyan Liu , Bo Yang

Three-dimensional generative models increasingly drive structure-based drug discovery, yet it remains constrained by the scarce publicly available protein-ligand complexes. Under such data scarcity, almost all existing pipelines struggle to…

Machine Learning · Computer Science 2025-08-15 Dong Xu , Zhangfan Yang , Jenna Xinyi Yao , Shuangbao Song , Zexuan Zhu , Junkai Ji

Molecular dynamics (MD) has long been the de facto choice for simulating complex atomistic systems from first principles. Recently deep learning models become a popular way to accelerate MD. Notwithstanding, existing models depend on…

Computational Engineering, Finance, and Science · Computer Science 2023-01-10 Fang Wu , Stan Z. Li

The efficacy of a drug depends on its binding affinity to the therapeutic target and pharmacokinetics. Deep learning (DL) has demonstrated remarkable progress in predicting drug efficacy. We develop MolDesigner, a human-in-the-loop web…

Quantitative Methods · Quantitative Biology 2020-10-09 Kexin Huang , Tianfan Fu , Dawood Khan , Ali Abid , Ali Abdalla , Abubakar Abid , Lucas M. Glass , Marinka Zitnik , Cao Xiao , Jimeng Sun

Finetuning a Large Language Model (LLM) is crucial for generating results towards specific objectives. This research delves into the realm of drug optimization and introduce a novel reinforcement learning algorithm to finetune a drug…

Machine Learning · Computer Science 2025-02-12 Xuefeng Liu , Songhao Jiang , Siyu Chen , Zhuoran Yang , Yuxin Chen , Ian Foster , Rick Stevens

When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize…

Machine Learning · Computer Science 2026-05-18 Ziyu Xu , Zijian Zhang , Liang Wang , Zhiyuan Liu , Qiang Liu , Shu Wu , Liang Wang

Uncertainties such as manufacturing tolerances cause performance variations in complex engineering systems, making robust design optimization (RDO) essential. However, simulation-based RDO faces high computational cost for statistical…

Optimization and Control · Mathematics 2026-02-10 Hyunho Jang , Dongjin Lee

Understanding the structure of the protein-ligand complex is crucial to drug development. Existing virtual structure measurement and screening methods are dominated by docking and its derived methods combined with deep learning. However,…

Artificial Intelligence · Computer Science 2024-08-22 Kelei He , Tiejun Dong , Jinhui Wu , Junfeng Zhang

Recent advancements in deep learning-based modeling of molecules promise to accelerate in silico drug discovery. A plethora of generative models is available, building molecules either atom-by-atom and bond-by-bond or fragment-by-fragment.…

Virtual screening can accelerate drug discovery by identifying promising candidates for experimental evaluation. Machine learning is a powerful method for screening, as it can learn complex structure-property relationships from experimental…

Machine Learning · Computer Science 2021-02-22 Simon Axelrod , Rafael Gomez-Bombarelli

Accurate identification of druggable pockets and their features is essential for structure-based drug design and effective downstream docking. Here, we present RAPID-Net, a deep learning-based algorithm designed for the accurate prediction…

Biomolecules · Quantitative Biology 2025-07-24 Yaroslav Balytskyi , Inna Hubenko , Alina Balytska , Christopher V. Kelly

One of the major applications of generative models for drug Discovery targets the lead-optimization phase. During the optimization of a lead series, it is common to have scaffold constraints imposed on the structure of the molecules…

Quantitative Methods · Quantitative Biology 2021-01-05 Maxime Langevin , Herve Minoux , Maximilien Levesque , Marc Bianciotto

This study proposes an acceleration technique for the computational challenges in extending the variational deterministic-particle-based scheme (VDS) [Bao et al., Journal of Computational Physics 522 (2025) 113589] to 3D complex fluid…

Computational Physics · Physics 2026-03-16 L. Fang , X. Bao , Z. Song , S. Xu , H. Huang

De novo molecule generation allows the search for more drug-like hits across a vast chemical space. However, lead optimization is still required, and the process of optimizing molecular structures faces the challenge of balancing structural…

Machine Learning · Computer Science 2026-05-12 Jiebin Fang , Churu Mao , Yuchen Zhu , Xiaoming Chen , Chang-Yu Hsieh , Zhongjun Ma

In a tie-breaker design (TBD), subjects with high values of a running variable are given some (usually desirable) treatment, subjects with low values are not, and subjects in the middle are randomized. TBDs are intermediate between…

Methodology · Statistics 2025-05-12 Tim P. Morrison , Art B. Owen

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu

There is a huge problem and time-consuming computation to optimize the IMRT treatment plan. Extracting the optimized plan from the predicted 3D3 so-called optimizing the KBP is also involved in this challenge. Some algorithms and methods…

Medical Physics · Physics 2023-06-28 Ali Yousefi , Saeedeh Ketabi , Iraj Abedi

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

We propose an adaptive design for early phase drug combination cancer trials with the goal of estimating the maximum tolerated dose (MTD). A nonparametric Bayesian model, using beta priors truncated to the set of partially ordered dose…

Applications · Statistics 2019-10-22 Zahra S. Razaee , Galen Wien-Cook , Mourad Tighiouart
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