使用机器学习预测鲁复合物的抗菌活性
Markus Orsi1, Boon Shing Loh2, Cheng Weng2
1Department of Chemistry, Biochemistry & Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
Angewandte Chemie (International ed. in English)
|December 13, 2023
概括
机器学习 (ML) 加快了对新型金属抗生素的发现,以对抗日益增长的抗菌素耐药性 (AMR). ML模型预测了活跃的复合体,实现了对MRSA的5.7倍高的命中率,而不是最初的化合物库.
科学领域:
- 药用化学 医学化学
- 计算化学计算化学
- 发现抗微生物药物 发现抗微生物药物
背景情况:
- 抗菌素耐药性 (AMR) 的上升需要新的抗生素开发管道.
- 金属复合物作为抗微生物药物表现有希望,但与有机分子相比,研究是有限的.
- 机器学习 (ML) 越来越多地用于小型有机分子设计,即使数据有限.
研究的目的:
- 首次将ML应用于发现金属基抗菌剂.
- 为了训练ML模型,使用烯希夫基复合物及其抗菌数据.
- 预测和验证新型金属基化合物的活性.
主要方法:
- 合成了288个鲁烯的希夫基复合物.
- 评估合成复合物的抗菌特性.
- 训练有素的ML模型对复合体及其活动的数据集.
- 使用训练的ML模型预测54种新化合物的活性.
主要成果:
- 机器学习模型表现出强大的预测性能.
- 与初始库 (9.4%) 相比,预测的化合物显示出对抗甲素耐药黄金葡萄球菌 (MRSA) 的成功率是5.7倍 (53.7%).
- 在识别有力金属抗生素方面成功应用ML.
结论:
- 在寻找新的金属抗生素方面,ML可以显著提高成功率.
- 这项研究证实了ML作为一种强大的金属药物发现工具.
- 在设计基于金属的药物中为更广泛的ML应用铺平了道路.
更多相关视频
07:12Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor
Published on: October 26, 2017
7.9K
08:46Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications
Published on: April 21, 2022
2.4K
相关概念视频
01:28Antimicrobial Effectiveness
The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
01:25Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...