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Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

The de novo design of molecular structures using deep learning generative models introduces an encouraging solution to drug discovery in the face of the continuously increased cost of new drug development. From the generation of original…

Biomolecules · Quantitative Biology 2021-02-08 Yuemin Bian , Xiang-Qun Xie

A molecule's geometry, also known as conformation, is one of a molecule's most important properties, determining the reactions it participates in, the bonds it forms, and the interactions it has with other molecules. Conventional…

Machine Learning · Computer Science 2020-01-01 Elman Mansimov , Omar Mahmood , Seokho Kang , Kyunghyun Cho

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

Biomolecules · Quantitative Biology 2019-08-02 Heng Ma , Debsindhu Bhowmik , Hyungro Lee , Matteo Turilli , Michael T. Young , Shantenu Jha , Arvind Ramanathan

Discrete Element Method (DEM) simulations of granular media are computationally intensive, particularly during initialization phases dominated by large displacements and kinetic energy. This paper presents a novel generative pipeline based…

Machine Learning · Computer Science 2026-03-23 Muhammad Moeeze Hassan , Régis Cottereau , Filippo Gatti , Patryk Dec

We develop revised theoretical ideas on the mechanism by which the transcription factor proteins locate their specific binding sites on DNA faster than the three-dimensional (3D) diffusion controlled rate limit. We demonstrate that the…

Biological Physics · Physics 2014-09-22 Rajamanickam Murugan

Protein function is often controlled by ligands that bias the direction of state transitions, such as agonists and antagonists, rather than stabilizing a single conformation. This is especially important for clinically relevant G…

Biomolecules · Quantitative Biology 2026-05-12 Hanqun Cao , Aastha Pal , Sophia Tang , Yinuo Zhang , Jingjie Zhang , Pheng Ann Heng , Pranam Chatterjee

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

Many crucial biological processes rely on networks of protein-protein interactions. Predicting the effect of amino acid mutations on protein-protein binding is vital in protein engineering and therapeutic discovery. However, the scarcity of…

Biomolecules · Quantitative Biology 2023-11-01 Shiwei Liu , Tian Zhu , Milong Ren , Chungong Yu , Dongbo Bu , Haicang Zhang

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Developing new molecular compounds is crucial to address pressing challenges, from health to environmental sustainability. However, exploring the molecular space to discover new molecules is difficult due to the vastness of the space. Here…

Machine Learning · Computer Science 2025-05-23 Manuel Ruiz-Botella , Marta Sales-Pardo , Roger Guimerà

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

A range of generative machine learning models for the design of novel molecules and materials have been proposed in recent years. Models that can generate three-dimensional structures are particularly suitable for quantum chemistry…

The Gaussian diffusion model, initially designed for image generation, has recently been adapted for 3D point cloud generation. However, these adaptations have not fully considered the intrinsic geometric characteristics of 3D shapes,…

Graphics · Computer Science 2024-08-01 Dengsheng Chen , Jie Hu , Xiaoming Wei , Enhua Wu

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high…

Biomolecules · Quantitative Biology 2022-09-28 John M McBride , Jean-Pierre Eckmann , Tsvi Tlusty

Drug targets are the main focus of drug discovery due to their key role in disease pathogenesis. Computational approaches are widely applied to drug development because of the increasing availability of biological molecular datasets.…

Machine Learning · Computer Science 2022-12-06 Junde Li , Collin Beaudoin , Swaroop Ghosh

Generative models for structure-based molecular design hold significant promise for drug discovery, with the potential to speed up the hit-to-lead development cycle, while improving the quality of drug candidates and reducing costs. Data…

Machine Learning · Statistics 2022-04-25 Lucian Chan , Rajendra Kumar , Marcel Verdonk , Carl Poelking

Diffusion-based generative models (DBGMs) perturb data to a target noise distribution and reverse this process to generate samples. The choice of noising process, or inference diffusion process, affects both likelihoods and sample quality.…

Machine Learning · Computer Science 2023-03-06 Raghav Singhal , Mark Goldstein , Rajesh Ranganath

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Diffusion probabilistic models have achieved remarkable success in text guided image generation. However, generating 3D shapes is still challenging due to the lack of sufficient data containing 3D models along with their descriptions.…

Computer Vision and Pattern Recognition · Computer Science 2023-08-08 Zijie Wu , Yaonan Wang , Mingtao Feng , He Xie , Ajmal Mian
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