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Due to the vast design space of molecules, generating molecules conditioned on a specific sub-structure relevant to a particular function or therapeutic target is a crucial task in computer-aided drug design. Existing works mainly focus on…

Biomolecules · Quantitative Biology 2024-12-24 Qi Zhengyang , Liu Zijing , Zhang Jiying , Cao He , Li Yu

Large language models (LLMs) show promise for molecular optimization, but aligning them with selective and competing drug-design constraints remains challenging. We propose C-Moral, a reinforcement learning post-training framework for…

Machine Learning · Computer Science 2026-05-28 Rui Gao , Youngseung Jeon , Swastik Roy , Morteza Ziyadi , Xiang 'Anthony' Chen

Bilevel optimization is characterized by a two-level optimization structure, where the upper-level problem is constrained by optimal lower-level solutions, and such structures are prevalent in real-world problems. The constraint by optimal…

Machine Learning · Computer Science 2025-05-29 Ruth Wan Theng Chew , Quoc Phong Nguyen , Bryan Kian Hsiang Low

Bayesian Optimization (BO) has shown great promise for the global optimization of functions that are expensive to evaluate, but despite many successes, standard approaches can struggle in high dimensions. To improve the performance of BO,…

Machine Learning · Computer Science 2022-06-17 Sebastian Ament , Carla Gomes

Generative molecular optimization aims to design molecules with properties surpassing those of existing compounds. However, such candidates are rare and expensive to evaluate, yielding sample efficiency essential. Additionally, surrogate…

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

A core challenge in structural biophysics is generating biomolecular conformations that are both physically plausible and consistent with experimental measurements. While sequence-to-structure diffusion models provide powerful priors,…

Machine Learning · Computer Science 2026-05-15 Minhuan Li , Jiequn Han , Pilar Cossio , Luhuan Wu

High-dimensional Bayesian optimization (BO) tasks such as molecular design often require 10,000 function evaluations before obtaining meaningful results. While methods like sparse variational Gaussian processes (SVGPs) reduce computational…

Machine Learning · Computer Science 2025-06-11 Natalie Maus , Kyurae Kim , Geoff Pleiss , David Eriksson , John P. Cunningham , Jacob R. Gardner

Many real-world tasks require optimizing expensive black-box functions accessible only through noisy evaluations, a setting commonly addressed with Bayesian optimization (BO). While Bayesian neural networks (BNNs) have recently emerged as…

Machine Learning · Computer Science 2026-01-14 Farhad Mirkarimi

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.…

Lead optimization is a pivotal task in the drug design phase within the drug discovery lifecycle. The primary objective is to refine the lead compound to meet specific molecular properties for progression to the subsequent phase of…

Biomolecules · Quantitative Biology 2024-07-22 Siddartha Reddy N , Sai Prakash MV , Varun V , Vishal Vaddina , Saisubramaniam Gopalakrishnan

Optimization of conflicting functions is of paramount importance in decision making, and real world applications frequently involve data that is uncertain or unknown, resulting in multi-objective optimization (MOO) problems of stochastic…

Numerical Analysis · Mathematics 2021-02-08 Suyun Liu , Luis Nunes Vicente

Molecular property optimization (MPO) problems are inherently challenging since they are formulated over discrete, unstructured spaces and the labeling process involves expensive simulations or experiments, which fundamentally limits the…

Biomolecules · Quantitative Biology 2024-01-04 Farshud Sorourifar , Thomas Banker , Joel A. Paulson

In recent years, a variety of gradient-based methods have been developed to solve Bi-Level Optimization (BLO) problems in machine learning and computer vision areas. However, the theoretical correctness and practical effectiveness of these…

Machine Learning · Computer Science 2022-01-04 Risheng Liu , Pan Mu , Xiaoming Yuan , Shangzhi Zeng , Jin Zhang

Multilevel optimization has gained renewed interest in machine learning due to its promise in applications such as hyperparameter tuning and continual learning. However, existing methods struggle with the inherent difficulty of efficiently…

Machine Learning · Computer Science 2024-10-16 Yuntian Gu , Xuzheng Chen

Artificial Intelligence predicts drug properties by encoding drug molecules, aiding in the rapid screening of candidates. Different molecular representations, such as SMILES and molecule graphs, contain complementary information for…

Machine Learning · Computer Science 2024-06-27 Muzhen Cai , Sendong Zhao , Haochun Wang , Yanrui Du , Zewen Qiang , Bing Qin , Ting Liu

Multi-objective optimization is central to many engineering and machine learning applications, where multiple objectives must be optimized in balance. While multi-gradient based optimization methods combine these objectives in each step,…

Optimization and Control · Mathematics 2026-05-13 Trang H. Tran , Luis Nunes Vicente

In this paper, we provide a novel analytical perspective on the theoretical understanding of gradient-based learning algorithms by interpreting consensus-based optimization (CBO), a recently proposed multi-particle derivative-free…

Machine Learning · Computer Science 2026-03-02 Konstantin Riedl , Timo Klock , Carina Geldhauser , Massimo Fornasier

Recently, multi-objective optimization (MOO) has gained attention for its broad applications in ML, operations research, and engineering. However, MOO algorithm design remains in its infancy and many existing MOO methods suffer from…

Machine Learning · Computer Science 2025-06-26 Zhuqing Liu , Chaosheng Dong , Michinari Momma , Simone Shao , Shaoyuan Xu , Yan Gao , Haibo Yang , Jia Liu

Combinatorial optimization problems have aroused extensive research interests due to its huge application potential. In practice, there are highly redundant patterns and characteristics during solving the combinatorial optimization problem,…

Optimization and Control · Mathematics 2022-02-22 Qingyu Qu , Xijun Li , Yunfan Zhou
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