鼠疫耶尔森菌二氢叶酸还原酶潜在新型抑制剂的虚拟筛选、对接及动力学研究
Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.
作者信息
Bastos Leonardo da Costa, de Souza Felipe Rodrigues, Guimarães Ana Paula, Sirouspour Mehdi, Cuya Guizado Teobaldo Ricardo, Forgione Pat, Ramalho Teodorico Castro, França Tanos Celmar Costa
机构信息
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.
b Department of Chemistry , Federal University of Viçosa , Viçosa , MG 36570-000 Brazil.
出版信息
J Biomol Struct Dyn. 2016 Oct;34(10):2184-98. doi: 10.1080/07391102.2015.1110832. Epub 2016 Jan 11.
In the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (DHFR) as a means of a novel drug therapy against plague. Potential inhibitors of DHFR from Yersinia pestis (YpDHFR) were selected by virtual screening and subjected to docking, molecular dynamics (MD) simulations, and Poisson-Boltzmann surface area method, in order to evaluate their interactions in the active sites of YpDHFR and human DHFR (HssDHFR). The results suggested selectivity for three compounds that were further used to propose the structures of six new potential selective inhibitors for YpDHFR.
在本研究中，我们提议设计靶向二氢叶酸还原酶（DHFR）的药物，作为一种针对鼠疫的新型药物治疗手段。通过虚拟筛选从鼠疫耶尔森菌（YpDHFR）中选择DHFR的潜在抑制剂，并进行对接、分子动力学（MD）模拟和泊松-玻尔兹曼表面积法，以评估它们在YpDHFR和人DHFR（HssDHFR）活性位点中的相互作用。结果表明对三种化合物具有选择性，这三种化合物进一步用于提出六种新的YpDHFR潜在选择性抑制剂的结构。
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