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Developing bioactive molecules remains a central, time- and cost-heavy challenge in drug discovery, particularly for novel targets lacking structural or functional data. Pharmacophore modeling presents an alternative for capturing the key…

Machine Learning · Computer Science 2025-05-16 Amira Alakhdar , Barnabas Poczos , Newell Washburn

A common starting point for drug design is to find small chemical groups or "fragments" that form interactions with distinct subregions in a protein binding pocket. The subsequent challenge is to assemble these fragments into a molecule…

Quantitative Methods · Quantitative Biology 2025-05-29 Rohan V. Koodli , Alexander S. Powers , Ayush Pandit , Chiho Im , Ron O. Dror

In the scope of drug discovery, the molecular design aims to identify novel compounds from the chemical space where the potential drug-like molecules are estimated to be in the order of 10^60 - 10^100. Since this search task is…

Machine Learning · Computer Science 2022-10-25 Wenlu Wang , Ye Wang , Honggang Zhao , Simone Sciabola

The fundamental goal of generative drug design is to propose optimized molecules that meet predefined activity, selectivity, and pharmacokinetic criteria. Despite recent progress, we argue that existing generative methods are limited in…

Chemical Physics · Physics 2020-12-17 Julien Horwood , Emmanuel Noutahi

Ligand-based drug design aims to identify novel drug candidates of similar shapes with known active molecules. In this paper, we formulated an in silico shape-conditioned molecule generation problem to generate 3D molecule structures…

Machine Learning · Computer Science 2023-10-18 Ziqi Chen , Bo Peng , Srinivasan Parthasarathy , Xia Ning

Biological systems commonly exhibit complex spatiotemporal patterns whose underlying generative mechanisms pose a significant analytical challenge. Traditional approaches to spatiodynamic inference rely on dimensionality reduction through…

Quantitative Methods · Quantitative Biology 2025-08-01 Jun Won Park , Kangyu Zhao , Sanket Rane

The widespread application of Artificial Intelligence (AI) techniques has significantly influenced the development of new therapeutic agents. These computational methods can be used to design and predict the properties of generated…

Neural and Evolutionary Computing · Computer Science 2024-08-21 Arthur Cerveira , Frederico Kremer , Darling de Andrade Lourenço , Ulisses B Corrêa

A common method for delineating urban and suburban boundaries is to identify clusters of spatial units that are highly interconnected in a network of commuting flows, each cluster signaling a cohesive economic submarket. It is critical that…

Physics and Society · Physics 2024-05-09 Sebastian Morel-Balbi , Alec Kirkley

Spatially resolved transcriptomics represents a significant advancement in single-cell analysis by offering both gene expression data and their corresponding physical locations. However, this high degree of spatial resolution entails a…

Genomics · Quantitative Biology 2024-03-19 Xiaoyu Li , Wenwen Min , Shunfang Wang , Changmiao Wang , Taosheng Xu

The process of screening molecules for desirable properties is a key step in several applications, ranging from drug discovery to material design. During the process of drug discovery specifically, protein-ligand docking, or chemical…

Machine Learning · Computer Science 2022-11-08 Ryien Hosseini , Filippo Simini , Austin Clyde , Arvind Ramanathan

Protein structure generative models excel at predicting single protein static structures from sequence, but routinely fail to capture the correct conformational state of protein complexes, critical for protein design and induced proximity…

Machine Learning · Computer Science 2026-05-27 Alon Shtrikman , Nitzan Simchi , Michal Ran Shchory , Sagie Brodsky , Eran Seger , Kirill Pevzner

In recent years, increasingly complex computational models are being built to describe physical systems which has led to increased use of surrogate models to reduce computational cost. In problems related to Structural Health Monitoring…

Machine Learning · Computer Science 2024-07-08 Nicholas E. Silionis , Theodora Liangou , Konstantinos N. Anyfantis

How to improve generative modeling by better exploiting spatial regularities and coherence in images? We introduce a novel neural network for building image generators (decoders) and apply it to variational autoencoders (VAEs). In our…

Computer Vision and Pattern Recognition · Computer Science 2021-03-17 Đorđe Miladinović , Aleksandar Stanić , Stefan Bauer , Jürgen Schmidhuber , Joachim M. Buhmann

Drug discovery is a complex, resource-intensive process requiring significant time and cost to bring new medicines to patients. Many generative models aim to accelerate drug discovery, but few produce synthetically accessible molecules.…

Machine Learning · Computer Science 2025-01-30 Zygimantas Jocys , Zhanxing Zhu , Henriette M. G. Willems , Katayoun Farrahi

Recently, deep generative models for molecular graphs are gaining more and more attention in the field of de novo drug design. A variety of models have been developed to generate topological structures of drug-like molecules, but…

Quantitative Methods · Quantitative Biology 2021-09-16 Yibo Li , Jianfeng Pei , Luhua Lai

Machine learning has the potential to automate molecular design and drastically accelerate the discovery of new functional compounds. Towards this goal, generative models and reinforcement learning (RL) using string and graph…

Machine Learning · Computer Science 2022-02-02 Daniel Flam-Shepherd , Alexander Zhigalin , Alán Aspuru-Guzik

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

High-dimensional imaging of neural activity, such as widefield calcium and functional ultrasound imaging, provide a rich source of information for understanding the relationship between brain activity and behavior. Accurately modeling…

Neurons and Cognition · Quantitative Biology 2025-09-24 Mohammad Hosseini , Maryam M. Shanechi

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

Effective training of deep neural networks suffers from two main issues. The first is that the parameter spaces of these models exhibit pathological curvature. Recent methods address this problem by using adaptive preconditioning for…

Machine Learning · Statistics 2015-12-25 Chunyuan Li , Changyou Chen , David Carlson , Lawrence Carin
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