Issue 6, 2023

SDEGen: learning to evolve molecular conformations from thermodynamic noise for conformation generation

Abstract

Generation of representative conformations for small molecules is a fundamental task in cheminformatics and computer-aided drug discovery, but capturing the complex distribution of conformations that contains multiple low energy minima is still a great challenge. Deep generative modeling, aiming to learn complex data distributions, is a promising approach to tackle the conformation generation problem. Here, inspired by stochastic dynamics and recent advances in generative modeling, we developed SDEGen, a novel conformation generation model based on stochastic differential equations. Compared with existing conformation generation methods, it enjoys the following advantages: (1) high model capacity to capture multimodal conformation distribution, thereby searching for multiple low-energy conformations of a molecule quickly, (2) higher conformation generation efficiency, almost ten times faster than the state-of-the-art score-based model, ConfGF, and (3) a clear physical interpretation to learn how a molecule evolves in a stochastic dynamics system starting from noise and eventually relaxing to the conformation that falls in low energy minima. Extensive experiments demonstrate that SDEGen has surpassed existing methods in different tasks for conformation generation, interatomic distance distribution prediction, and thermodynamic property estimation, showing great potential for real-world applications.

Graphical abstract: SDEGen: learning to evolve molecular conformations from thermodynamic noise for conformation generation

Supplementary files

Article information

Article type
Edge Article
Submitted
09 Aug 2022
Accepted
11 Jan 2023
First published
12 Jan 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 1557-1568

SDEGen: learning to evolve molecular conformations from thermodynamic noise for conformation generation

H. Zhang, S. Li, J. Zhang, Z. Wang, J. Wang, D. Jiang, Z. Bian, Y. Zhang, Y. Deng, J. Song, Y. Kang and T. Hou, Chem. Sci., 2023, 14, 1557 DOI: 10.1039/D2SC04429C

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