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Sculpting molecules in text-3D space: a flexible substructure aware framework for text-oriented molecular optimization.

作者信息

Zhang Kaiwei, Lin Yange, Wu Guangcheng, Ren Yuxiang, Zhang Xuecang, Wang Bo, Zhang Xiao-Yu, Du Weitao

机构信息

Institute of Information Engineering, Chinese Academy of Sciences, Beijing, 100085, China.

Huawei Technologies, Shenzhen, China.

出版信息

BMC Bioinformatics. 2025 May 7;26(1):123. doi: 10.1186/s12859-025-06072-w.


DOI:10.1186/s12859-025-06072-w
PMID:40335938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12060419/
Abstract

The integration of deep learning, particularly AI-Generated Content, with high-quality data derived from ab initio calculations has emerged as a promising avenue for transforming the landscape of scientific research. However, the challenge of designing molecular drugs or materials that incorporate multi-modality prior knowledge remains a critical and complex undertaking. Specifically, achieving a practical molecular design necessitates not only meeting the diversity requirements but also addressing structural and textural constraints with various symmetries outlined by domain experts. In this article, we present an innovative approach to tackle this inverse design problem by formulating it as a multi-modality guidance optimization task. Our proposed solution involves a textural-structure alignment symmetric diffusion framework for the implementation of molecular optimization tasks, namely 3DToMolo. 3DToMolo aims to harmonize diverse modalities including textual description features and graph structural features, aligning them seamlessly to produce molecular structures adhere to specified symmetric structural and textural constraints by experts in the field. Experimental trials across three guidance optimization settings have shown a superior hit optimization performance compared to state-of-the-art methodologies. Moreover, 3DToMolo demonstrates the capability to discover potential novel molecules, incorporating specified target substructures, without the need for prior knowledge. This work not only holds general significance for the advancement of deep learning methodologies but also paves the way for a transformative shift in molecular design strategies. 3DToMolo creates opportunities for a more nuanced and effective exploration of the vast chemical space, opening new frontiers in the development of molecular entities with tailored properties and functionalities.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/4b60b03e3965/12859_2025_6072_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/f694cc33f9f5/12859_2025_6072_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/a0871f85b6c2/12859_2025_6072_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/fe8bd3e9f3a7/12859_2025_6072_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/6bff1cef2c5b/12859_2025_6072_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/07059af46a7e/12859_2025_6072_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/4b60b03e3965/12859_2025_6072_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/f694cc33f9f5/12859_2025_6072_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/a0871f85b6c2/12859_2025_6072_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/fe8bd3e9f3a7/12859_2025_6072_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/6bff1cef2c5b/12859_2025_6072_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/07059af46a7e/12859_2025_6072_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bea1/12060419/4b60b03e3965/12859_2025_6072_Fig6_HTML.jpg

相似文献

[1]
Sculpting molecules in text-3D space: a flexible substructure aware framework for text-oriented molecular optimization.

BMC Bioinformatics. 2025-5-7

[2]
Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

Phys Biol. 2013-8

[3]
Boosting the performance of molecular property prediction via graph-text alignment and multi-granularity representation enhancement.

J Mol Graph Model. 2024-11

[4]
Equivariant score-based generative diffusion framework for 3D molecules.

BMC Bioinformatics. 2024-5-30

[5]
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[6]
Proceedings of the Second Workshop on Theory meets Industry (Erwin-Schrödinger-Institute (ESI), Vienna, Austria, 12-14 June 2007).

J Phys Condens Matter. 2008-2-13

[7]
FSM-DDTR: End-to-end feedback strategy for multi-objective De Novo drug design using transformers.

Comput Biol Med. 2023-9

[8]
Revisiting Pyrimidine-Embedded Molecular Frameworks to Probe the Unexplored Chemical Space for Protein-Protein Interactions.

Acc Chem Res. 2024-11-19

[9]
Enhancing Molecular Property Prediction through Task-Oriented Transfer Learning: Integrating Universal Structural Insights and Domain-Specific Knowledge.

J Med Chem. 2024-6-13

[10]
Activity cliff-aware reinforcement learning for de novo drug design.

J Cheminform. 2025-4-21

本文引用的文献

[1]
Drug Design Using Reinforcement Learning with Graph-Based Deep Generative Models.

J Chem Inf Model. 2022-10-24

[2]
A Deep Generative Model for Molecule Optimization via One Fragment Modification.

Nat Mach Intell. 2021-12

[3]
A deep-learning system bridging molecule structure and biomedical text with comprehension comparable to human professionals.

Nat Commun. 2022-2-14

[4]
Structure-Based Drug Design Using Deep Learning.

J Chem Inf Model. 2022-11-14

[5]
Structure-based drug design using 3D deep generative models.

Chem Sci. 2021-9-9

[6]
MolGPT: Molecular Generation Using a Transformer-Decoder Model.

J Chem Inf Model. 2022-5-9

[7]
Masked graph modeling for molecule generation.

Nat Commun. 2021-5-26

[8]
Molecular optimization by capturing chemist's intuition using deep neural networks.

J Cheminform. 2021-3-20

[9]
Randomized SMILES strings improve the quality of molecular generative models.

J Cheminform. 2019-11-21

[10]
A de novo molecular generation method using latent vector based generative adversarial network.

J Cheminform. 2019-12-3

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