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极光激酶A-TPX2蛋白-蛋白相互作用小分子抑制剂的计算引导优化

Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.

作者信息

Cole Daniel J, Janecek Matej, Stokes Jamie E, Rossmann Maxim, Faver John C, McKenzie Grahame J, Venkitaraman Ashok R, Hyvönen Marko, Spring David R, Huggins David J, Jorgensen William L

机构信息

Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA and School of Chemistry, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.

MRC Cancer Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK and Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

出版信息

Chem Commun (Camb). 2017 Aug 17;53(67):9372-9375. doi: 10.1039/c7cc05379g.

DOI:10.1039/c7cc05379g
PMID:28787041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5591577/
Abstract

Free energy perturbation theory, in combination with enhanced sampling of protein-ligand binding modes, is evaluated in the context of fragment-based drug design, and used to design two new small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.

摘要

在基于片段的药物设计背景下，对结合蛋白质-配体结合模式增强采样的自由能微扰理论进行了评估，并用于设计两种新型小分子抑制剂，以抑制极光激酶A（Aurora A kinase）与TPX2蛋白之间的蛋白质-蛋白质相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/6233e71bbc7b/c7cc05379g-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/79209638d9ca/c7cc05379g-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/a0efa0c9f3b4/c7cc05379g-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/84dd6f301b56/c7cc05379g-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/c5baeecb471c/c7cc05379g-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/6233e71bbc7b/c7cc05379g-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/79209638d9ca/c7cc05379g-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/a0efa0c9f3b4/c7cc05379g-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/84dd6f301b56/c7cc05379g-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/c5baeecb471c/c7cc05379g-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/5933003/6233e71bbc7b/c7cc05379g-f5.jpg

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1
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J Chem Theory Comput. 2016 Sep 13;12(9):4620-31. doi: 10.1021/acs.jctc.6b00532. Epub 2016 Aug 16.
2
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Sci Rep. 2016 Jun 24;6:28528. doi: 10.1038/srep28528.
3
Accurate Binding Free Energy Predictions in Fragment Optimization.在碎片优化中进行准确的结合自由能预测。
Cell Chem Biol. 2021 Jun 17;28(6):835-847.e5. doi: 10.1016/j.chembiol.2021.02.006. Epub 2021 Mar 3.
4
Exploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: A case study in polypharmacology.二氢乳清酸脱氢酶 (DHODH) 和 p53 激活的开发作为治疗靶点：多药理学的案例研究。
J Biol Chem. 2020 Dec 25;295(52):17935-17949. doi: 10.1074/jbc.RA119.012056. Epub 2020 Sep 8.
5
Optimization of Protein-Ligand Electrostatic Interactions Using an Alchemical Free-Energy Method.利用变分自由能方法优化蛋白-配体静电相互作用。
J Chem Theory Comput. 2019 Nov 12;15(11):6504-6512. doi: 10.1021/acs.jctc.9b00976. Epub 2019 Oct 23.
6
Computation of protein-ligand binding free energies using quantum mechanical bespoke force fields.使用量子力学定制力场计算蛋白质-配体结合自由能。
Medchemcomm. 2019 Feb 27;10(7):1116-1120. doi: 10.1039/c9md00017h. eCollection 2019 Jul 1.
J Chem Inf Model. 2015 Nov 23;55(11):2411-20. doi: 10.1021/acs.jcim.5b00538. Epub 2015 Oct 21.
4
Selective Targeting of the TPX2 Site of Importin-α Using Fragment-Based Ligand Design.基于片段的配体设计对输入蛋白α的TPX2位点进行选择性靶向
ChemMedChem. 2015 Jul;10(7):1232-9. doi: 10.1002/cmdc.201500014. Epub 2015 Apr 20.
5
Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor.作为巨噬细胞迁移抑制因子有效互变异构酶抑制剂的联芳基三唑的设计、合成及蛋白质晶体学研究
J Am Chem Soc. 2015 Mar 4;137(8):2996-3003. doi: 10.1021/ja512112j. Epub 2015 Feb 20.
6
Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.用于蛋白质-配体结合及抑制剂设计的分子动力学和蒙特卡洛模拟
Biochim Biophys Acta. 2015 May;1850(5):966-971. doi: 10.1016/j.bbagen.2014.08.018. Epub 2014 Sep 6.
7
Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering.通过溶质回火复制交换实现增强型蒙特卡罗采样。
J Chem Theory Comput. 2014 Feb 11;10(2):565-571. doi: 10.1021/ct400989x. Epub 2014 Jan 17.
8
The aurora kinases in cell cycle and leukemia.细胞周期与白血病中的极光激酶
Oncogene. 2015 Jan 29;34(5):537-45. doi: 10.1038/onc.2014.14. Epub 2014 Mar 17.
9
On achieving high accuracy and reliability in the calculation of relative protein-ligand binding affinities.实现相对蛋白质-配体结合亲和力计算的高精度和高可靠性。
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):1937-42. doi: 10.1073/pnas.1114017109. Epub 2012 Jan 23.
10
Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents.通过计算指导对对接命中物的优化，得到儿茶酚二醚类作为有效的抗 HIV 药物。
J Med Chem. 2011 Dec 22;54(24):8582-91. doi: 10.1021/jm201134m. Epub 2011 Nov 29.