• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

共识和整体对接策略的结合在人源二氢乳清酸脱氢酶抑制剂发现中的应用。

Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors.

机构信息

Institute of Molecular Biology of NAS RA, 0014, Yerevan, Armenia.

Russian-Armenian University, 0051, Yerevan, Armenia.

出版信息

Sci Rep. 2021 Jun 1;11(1):11417. doi: 10.1038/s41598-021-91069-7.

DOI:10.1038/s41598-021-91069-7
PMID:34075175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8169699/
Abstract

The inconsistencies in the performance of the virtual screening (VS) process, depending on the used software and structural conformation of the protein, is a challenging issue in the drug design and discovery field. Varying performance, especially in terms of early recognition of the potential hit compounds, negatively affects the whole process and leads to unnecessary waste of the time and resources. Appropriate application of the ensemble docking and consensus-scoring approaches can significantly increase reliability of the VS results. Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the pyrimidine biosynthesis pathway. It is considered as a valuable therapeutic target in cancer, autoimmune and viral diseases. Based on the conducted benchmark study and analysis of the effect of different combinations of the applied methods and approaches, here we suggested a structure-based virtual screening (SBVS) workflow that can be used to increase the reliability of VS.

摘要

虚拟筛选 (VS) 过程的性能不一致，取决于所用的软件和蛋白质的结构构象，这是药物设计和发现领域的一个具有挑战性的问题。性能的变化，特别是在潜在命中化合物的早期识别方面，会对整个过程产生负面影响，并导致不必要的时间和资源浪费。适当应用集合对接和共识评分方法可以显著提高 VS 结果的可靠性。二氢乳清酸脱氢酶 (DHODH) 是嘧啶生物合成途径中的关键酶。它被认为是癌症、自身免疫和病毒疾病的有价值的治疗靶点。基于进行的基准研究和对应用方法和方法的不同组合的效果的分析，我们在这里提出了一种基于结构的虚拟筛选 (SBVS) 工作流程，可以用于提高 VS 的可靠性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/5139b583bb94/41598_2021_91069_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/a776e5720c36/41598_2021_91069_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/0a8bc15ec796/41598_2021_91069_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/7e280e954499/41598_2021_91069_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/7b5318d42a54/41598_2021_91069_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/a65abf75c6f9/41598_2021_91069_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/9503a6d599b1/41598_2021_91069_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/0ca539a07cfb/41598_2021_91069_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/5139b583bb94/41598_2021_91069_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/a776e5720c36/41598_2021_91069_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/0a8bc15ec796/41598_2021_91069_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/7e280e954499/41598_2021_91069_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/7b5318d42a54/41598_2021_91069_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/a65abf75c6f9/41598_2021_91069_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/9503a6d599b1/41598_2021_91069_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/0ca539a07cfb/41598_2021_91069_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acb/8169699/5139b583bb94/41598_2021_91069_Fig8_HTML.jpg

相似文献

1
Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors.共识和整体对接策略的结合在人源二氢乳清酸脱氢酶抑制剂发现中的应用。
Sci Rep. 2021 Jun 1;11(1):11417. doi: 10.1038/s41598-021-91069-7.
2
Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases.基于结构的人类和恶性疟原虫二氢乳清酸脱氢酶抑制剂的设计、合成与表征
J Med Chem. 2009 May 14;52(9):2683-93. doi: 10.1021/jm800963t.
3
Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors.二氢乳清酸脱氢酶（DHODH）抑制剂的药物化学和治疗潜力的最新进展。
Mini Rev Med Chem. 2011 Oct;11(12):1039-55. doi: 10.2174/138955711797247707.
4
The role of fluorine in stabilizing the bioactive conformation of dihydroorotate dehydrogenase inhibitors.氟在稳定二氢乳清酸脱氢酶抑制剂的生物活性构象中的作用。
J Mol Model. 2013 Mar;19(3):1099-107. doi: 10.1007/s00894-012-1643-5. Epub 2012 Nov 10.
5
Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study.基于药效基团的虚拟筛选研究鉴定人二氢乳清酸脱氢酶抑制剂。
Molecules. 2022 Jun 7;27(12):3660. doi: 10.3390/molecules27123660.
6
Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y strain.克氏锥虫Y株二氢乳清酸脱氢酶的晶体结构
Biochem Biophys Res Commun. 2008 May 9;369(3):812-7. doi: 10.1016/j.bbrc.2008.02.074. Epub 2008 Feb 25.
7
An in silico Workflow that Yields Experimentally Comparable Inhibitors for Human Dihydroorotate Dehydrogenase.一种可产生与人类二氢乳清酸脱氢酶具有实验可比性抑制剂的计算工作流程。
Curr Comput Aided Drug Des. 2020;16(3):340-350. doi: 10.2174/1573409915666190528114703.
8
A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode.通过体外筛选发现的一系列新型人二氢乳清酸脱氢酶抑制剂：抑制活性和晶体结合模式。
FEBS Open Bio. 2019 Aug;9(8):1348-1354. doi: 10.1002/2211-5463.12658. Epub 2019 May 29.
9
Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery.新型别构调节型 1 类二氢乳清酸脱氢酶抑制剂的研究进展
Eur J Med Chem. 2010 Dec;45(12):5899-909. doi: 10.1016/j.ejmech.2010.09.055. Epub 2010 Oct 7.
10
Development of a human dihydroorotate dehydrogenase (hDHODH) pharma-similarity index approach with scaffold-hopping strategy for the design of novel potential inhibitors.开发一种具有骨架跃迁策略的人二氢乳清酸脱氢酶（hDHODH）药物相似性指数方法，用于设计新型潜在抑制剂。
PLoS One. 2014 Feb 4;9(2):e87960. doi: 10.1371/journal.pone.0087960. eCollection 2014.

引用本文的文献

1
A computational framework for identifying chemical compounds to bind Apolipoprotein E4 for Alzheimer's disease intervention.一种用于识别与载脂蛋白E4结合以干预阿尔茨海默病的化合物的计算框架。
Front Syst Biol. 2023 Jun 14;3:1188430. doi: 10.3389/fsysb.2023.1188430. eCollection 2023.
2
Repurposing FDA-Approved Drugs Against Potential Drug Targets Involved in Brain Inflammation Contributing to Alzheimer's Disease.重新利用美国食品药品监督管理局（FDA）批准的药物，针对参与导致阿尔茨海默病的脑部炎症的潜在药物靶点。
Targets (Basel). 2024 Dec;2(4):446-469. doi: 10.3390/targets2040025. Epub 2024 Dec 4.
3
A human metabolic map of pharmacological perturbations reveals drug modes of action.

本文引用的文献

1
IMU-838, a Developmental DHODH Inhibitor in Phase II for Autoimmune Disease, Shows Anti-SARS-CoV-2 and Broad-Spectrum Antiviral Efficacy In Vitro.在研 DHODH 抑制剂 IMU-838 治疗自身免疫性疾病进入 II 期，在体外显示出抗 SARS-CoV-2 和广谱抗病毒活性。
Viruses. 2020 Dec 5;12(12):1394. doi: 10.3390/v12121394.
2
Potential treatment of COVID-19 by inhibitors of human dihydroorotate dehydrogenase.人二氢乳清酸脱氢酶抑制剂对新型冠状病毒肺炎的潜在治疗作用
Protein Cell. 2020 Oct;11(10):699-702. doi: 10.1007/s13238-020-00769-9.
3
Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.
一份药理学扰动的人类代谢图谱揭示了药物作用模式。
Nat Biotechnol. 2025 Jan 28. doi: 10.1038/s41587-024-02524-5.
4
Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation.靶向严重急性呼吸综合征冠状病毒2主要蛋白酶：一种采用先进虚拟筛选、分子动力学和体外验证的综合方法
Virol J. 2024 Dec 21;21(1):330. doi: 10.1186/s12985-024-02607-4.
5
Computational evaluation and benchmark study of 342 crystallographic holo-structures of SARS-CoV-2 Mpro enzyme.计算评估和 342 个 SARS-CoV-2 Mpro 酶晶体全息结构的基准研究。
Sci Rep. 2024 Jun 20;14(1):14255. doi: 10.1038/s41598-024-65228-5.
6
Comprehensive Survey of Consensus Docking for High-Throughput Virtual Screening.高通量虚拟筛选共识对接综合调查。
Molecules. 2022 Dec 25;28(1):175. doi: 10.3390/molecules28010175.
7
Combination of ligand and structure based virtual screening approaches for the discovery of potential PARP1 inhibitors.基于配体和结构的虚拟筛选方法结合用于发现潜在的 PARP1 抑制剂。
PLoS One. 2022 Sep 12;17(9):e0272065. doi: 10.1371/journal.pone.0272065. eCollection 2022.
8
Identification of Novel Potential VEGFR-2 Inhibitors Using a Combination of Computational Methods for Drug Discovery.运用多种药物发现计算方法鉴定新型潜在血管内皮生长因子受体-2（VEGFR-2）抑制剂
Life (Basel). 2021 Oct 11;11(10):1070. doi: 10.3390/life11101070.
9
Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery.使用药物设计和发现的计算方法组合鉴定非经典 hCA XII 抑制剂。
Sci Rep. 2021 Jul 30;11(1):15516. doi: 10.1038/s41598-021-94809-x.
新型、强效二氢乳清酸脱氢酶（DHODH）抑制剂是广谱抗 RNA 病毒药物，可针对包括新型冠状病毒 SARS-CoV-2 在内的多种 RNA 病毒。
Protein Cell. 2020 Oct;11(10):723-739. doi: 10.1007/s13238-020-00768-w. Epub 2020 Aug 4.
4
Structure-Based Virtual Screening: From Classical to Artificial Intelligence.基于结构的虚拟筛选：从经典方法到人工智能
Front Chem. 2020 Apr 28;8:343. doi: 10.3389/fchem.2020.00343. eCollection 2020.
5
Cross-docking benchmark for automated pose and ranking prediction of ligand binding.配体结合的自动构象和排序预测的交叉对接基准
Protein Sci. 2020 Jan;29(1):298-305. doi: 10.1002/pro.3784. Epub 2019 Nov 28.
6
Ensemble docking-based virtual screening toward identifying inhibitors against Wee1 kinase.基于集合对接的虚拟筛选鉴定 Wee1 激酶抑制剂
Future Med Chem. 2019 Aug;11(15):1889-1906. doi: 10.4155/fmc-2019-0022.
7
Comparison of Data Fusion Methods as Consensus Scores for Ensemble Docking.数据融合方法比较作为集合对接的共识评分。
Molecules. 2019 Jul 24;24(15):2690. doi: 10.3390/molecules24152690.
8
Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database.我们还能相信对接结果吗？DockBench 在 PDBbind 数据库上适用性的扩展。
Int J Mol Sci. 2019 Jul 20;20(14):3558. doi: 10.3390/ijms20143558.
9
Exponential consensus ranking improves the outcome in docking and receptor ensemble docking.指数一致排名可改善对接和受体组合对接的结果。
Sci Rep. 2019 Mar 26;9(1):5142. doi: 10.1038/s41598-019-41594-3.
10
Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer.重新审视二氢乳清酸脱氢酶作为癌症治疗靶点的作用。
Pharmacol Ther. 2019 Mar;195:111-131. doi: 10.1016/j.pharmthera.2018.10.012. Epub 2018 Oct 19.