发现一种具有可解释深度学习的抗生素结构类
Felix Wong1,2,3, Erica J Zheng1,4,5, Jacqueline A Valeri1,2,5
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|December 20, 2023
概括
研究人员开发了一种可解释的深度学习方法来发现新的抗生素结构类. 这种方法可以识别关键的化学基质,从而产生对MRSA等耐药细菌有效的新型抗生素.
科学领域:
- 医学化学
- 计算生物学
- 药物发现
背景情况:
- 抗生素耐药性是全球严重的健康威胁,
- 目前用于药物发现的深度学习模型通常充当黑子, 缺乏化学解释性.
- 识别与抗生素活性相关的特定化学子结构对于合理的药物设计至关重要.
研究的目的:
- 为发现新型抗生素类型开发一种可解释的,基于子结构的深度学习方法.
- 确定与高抗生素活性和低细胞毒性相关的化学基结构.
- 引导对潜在药物候选物的大量化学空间的探索.
主要方法:
- 对39312种化合物的抗生素活性和细胞毒性进行了查.
- 应用图形神经网络来预测超过 1200 万种化合物的活性和细胞毒性.
- 使用可解释的图形算法来识别结构-活性关系和抗生素潜力的理由.
主要成果:
- 确定了与强抗生素活性和低细胞毒性相关的特定化学基结构.
- 经验证实了283种化合物,在预测的抗生素结构类中发现了丰富性.
- 在小鼠感染模型中发现了一种针对抗甲基金色葡萄球菌 (MRSA) 和抗菌素肠球菌的新型化合物.
结论:
- 开发的可解释人工智能方法有效指导新型抗生素结构类的发现.
- 机器学习模型在药物发现中可以被解释,提供有价值的化学见解.
- 这种方法加速了对抗耐药性急需的抗生素的鉴定.
更多相关视频
09:08From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
17.2K
09:34A Virtual Machine Platform for Non-Computer Professionals for Using Deep Learning to Classify Biological Sequences of Metagenomic Data
Published on: September 25, 2021
4.0K
相关概念视频
Antibiotic Selection
53.9K
Overview
53.9K
Combined Effects of Drugs: Synergism
3.9K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.9K
Antimicrobial Proteins
998
Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
998
Defense Against Bacterial Pathogens
1.4K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
1.4K
