使用基于机器学习的虚拟查,ADMET分析,分子对接和分子动力学模拟来识别SARS-CoV-2目标3CLpro的抑制剂
Sandeep Poudel Chhetri1, Vishal Singh Bhandari2, Rajesh Maharjan1
1Central Department of Physics, Tribhuvan University Kathmandu 44600 Nepal tika.lamichhane@cdp.tu.edu.np.
RSC advances
|September 19, 2024
概括
我们通过使用机器学习来选数百万种化合物,确定了一种新型化合物M1,作为潜在的COVID-19治疗方法. M1显示出有前途的稳定性,安全性和结合性亲和力,需要进一步调查SARS-CoV-2治疗.
科学领域:
- 计算化学和药物发现
- 机器学习在药理学中的应用.
- 病毒学和传染病研究.
背景情况:
- SARS-CoV-2 3CLpro酶对于病毒复制至关重要,也是COVID-19治疗的关键标.
- 现有的治疗查方法可以通过整合机器学习和相似性分析来增强.
研究的目的:
- 用机器学习驱动的查管道识别SARS-CoV-2 3CLpro的新型抑制剂.
- 评估已识别的化合物,特别是M1,作为SARS-CoV-2治疗药物的潜力.
主要方法:
- 开发了一个投票分类器组合模型,以选大约1000万种化合物潜在的3CLpro抑制剂.
- 选择的化合物经过了吸收,分布,新陈代谢,分泌和毒性 (ADMET) 分析,分子对接和分子动力学 (MD) 模拟.
- 使用分子力学Poisson-Boltzmann表面积 (MM-PBSA) 估计了结合的自由能量.
主要成果:
- 整体机器学习模型成功过了大型化合物数据库,确定了三种潜在的抑制剂:M1,M2和M3.
- 与对照组相比,M1化合物在200 ns的MD模拟中表现出优越的稳定性.
- M1表现出有利的预测抑制活性,安全概况 (中位致命剂量,最大耐受剂量) 和强大的结合自由能量 (-18.86 ± 4.38 kcal mol-1).
结论:
- 化合物M1显示显著的希望作为潜在的治疗剂对抗SARS-CoV-2.
- 综合机器学习和计算分析方法在识别新药候选药物方面是有效的.
- 对M1进行进一步的临床前和临床研究是有必要的,以便其作为COVID-19治疗方法的开发.
更多相关视频
10:21Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
Published on: February 23, 2024
2.4K
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
461
相关概念视频
02:40Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
02:04Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K