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Electron density prediction stands as a cornerstone challenge in molecular systems, pivotal for various applications such as understanding molecular interactions and conducting precise quantum mechanical calculations. However, the scaling…

Chemical Physics · Physics 2024-10-10 Ilan Mitnikov , Joseph Jacobson

The generation of accurate 3D molecular conformations is a pivotal challenge in computational chemistry and drug discovery. Recently, diffusion and flow matching models have achieved remarkable success. However, there is a critical…

Machine Learning · Computer Science 2026-05-26 Yunqing Liu , Yi Zhou , Wenqi Fan

Energy-Based Models (EBMs) have proven to be a highly effective approach for modelling densities on finite-dimensional spaces. Their ability to incorporate domain-specific choices and constraints into the structure of the model through…

Machine Learning · Computer Science 2023-02-24 Jen Ning Lim , Sebastian Vollmer , Lorenz Wolf , Andrew Duncan

Recent advances in molecular generative models have demonstrated great promise for accelerating scientific discovery, particularly in drug design. However, these models often struggle to generate high-quality molecules, especially in…

Machine Learning · Computer Science 2025-07-29 Zian Li , Cai Zhou , Xiyuan Wang , Xingang Peng , Muhan Zhang

Retrosynthesis -- the process of identifying a set of reactants to synthesize a target molecule -- is of vital importance to material design and drug discovery. Existing machine learning approaches based on language models and graph neural…

Chemical Physics · Physics 2021-12-10 Ruoxi Sun , Hanjun Dai , Li Li , Steven Kearnes , Bo Dai

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the…

Numerical Analysis · Mathematics 2016-11-03 Guo-Wei Wei , Y. C. Zhou

We investigate the construction of generative models capable of encoding physical constraints that can be hard to express explicitly. For the problem of inverse material design, where one seeks to design a material with a prescribed set of…

Materials Science · Physics 2024-01-17 Khalid El-Awady

The dipole moment is a physical quantity indicating the polarity of a molecule and is determined by reflecting the electrical properties of constituent atoms and the geometric properties of the molecule. Most embeddings used to represent…

Machine Learning · Computer Science 2022-06-28 Yang Jeong Park

We introduce a guided stochastic sampling method that augments sampling from diffusion models with physics-based guidance derived from partial differential equation (PDE) residuals and observational constraints, ensuring generated samples…

Machine Learning · Computer Science 2026-05-28 Andrew Millard , Fredrik Lindsten , Zheng Zhao

The ultimate goal of drug design is to find novel compounds with desirable pharmacological properties. Designing molecules retaining particular scaffolds as the core structures of the molecules is one of the efficient ways to obtain…

Quantitative Methods · Quantitative Biology 2019-09-06 Yibo Li , Jianxing Hu , Yanxing Wang , Jielong Zhou , Liangren Zhang , Zhenming Liu

We consider optimal experimental design (OED) for Bayesian nonlinear inverse problems governed by partial differential equations (PDEs) under model uncertainty. Specifically, we consider inverse problems in which, in addition to the…

Numerical Analysis · Mathematics 2024-07-03 Alen Alexanderian , Ruanui Nicholson , Noemi Petra

Molecular modeling, a central topic in quantum mechanics, aims to accurately calculate the properties and simulate the behaviors of molecular systems. The molecular model is governed by physical laws, which impose geometric constraints such…

Machine Learning · Computer Science 2024-06-25 Tianlang Chen , Shengjie Luo , Di He , Shuxin Zheng , Tie-Yan Liu , Liwei Wang

Computational methods that operate on three-dimensional molecular structure have the potential to solve important questions in biology and chemistry. In particular, deep neural networks have gained significant attention, but their…

We report a method to convert discrete representations of molecules to and from a multidimensional continuous representation. This model allows us to generate new molecules for efficient exploration and optimization through open-ended…

Constructing accurate, high dimensional molecular potential energy surfaces (PESs) for polyatomic molecules is challenging. Reproducing Kernel Hilbert space (RKHS) interpolation is an efficient way to construct such PESs. However, the…

Chemical Physics · Physics 2020-11-06 Debasish Koner , Markus Meuwly

Recent advances in Structure-based Drug Design (SBDD) have leveraged generative models for 3D molecular generation, predominantly evaluating model performance by binding affinity to target proteins. However, practical drug discovery…

The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

Optimizing chemical properties is a challenging task due to the vastness and complexity of chemical space. Here, we present a generative energy-based architecture for implicit chemical property optimization, designed to efficiently generate…

Biomolecules · Quantitative Biology 2025-06-19 Luca Miglior , Lorenzo Simone , Marco Podda , Davide Bacciu

Diffusion-based generative models employ stochastic differential equations (SDEs) and their equivalent probability flow ordinary differential equations (ODEs) to establish a smooth transformation between complex high-dimensional data…

Machine Learning · Computer Science 2025-12-12 Defang Chen , Zhenyu Zhou , Can Wang , Siwei Lyu

In the field of Structure-based Drug Design (SBDD), deep learning-based generative models have achieved outstanding performance in terms of docking score. However, further study shows that the existing molecular generative methods and…

Biomolecules · Quantitative Biology 2024-03-21 Bowen Gao , Minsi Ren , Yuyan Ni , Yanwen Huang , Bo Qiang , Zhi-Ming Ma , Wei-Ying Ma , Yanyan Lan
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