Studies on the interactions of Ti-containing polyoxometalates (POMs) with SARS-CoV 3CLpro by molecular modeling
Studies on the interactions of Ti-containing polyoxometalates (POMs) with SARS-CoV 3CLpro by molecular modeling
复制标题
通过分子模型研究含钛多金属氧酸盐（POM）与 SARS-CoV 3CLpro 的相互作用
DOI：
10.1016/j.jinorgbio.2006.08.013
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发表时间：
2007-01-01
影响因子：
3.9
通讯作者：
Sun, Jiazhong
中科院分区：
文献类型：
--
作者：
Hu, Donghua;Shao, Chen;Sun, Jiazhong
含钛的α-Keggin多氧杂环丁烷酸盐（POM）具有抗肿瘤和抗HIV（人类免疫缺陷病毒）的双重活性。本文采用分子模拟方法研究了多金属氧酸盐[α-PTi_2 W_（10）O_（40）]（7-）异构体的抗SARS活性。SARS 3c样蛋白酶（SARS 3CL（pro））是病毒复制和转录的关键功能蛋白酶，可作为抗SARS药物设计的关键靶点之一。亲和力/洞察II用于探索POM/3CL（pro）相互作用的可能结合位置。用密度泛函理论（DFT）方法计算了POM中的电荷。结果表明：POMs与3CL（pro）在活性中心区域以高亲和力结合; POMs与3CL（pro）的结合比与某些有机物的结合更容易;对于POMs/3CL（pro）复合物，POMs中的OTi 2是静电相互作用的关键元素，其静电结合能足以维持复合物的稳定性。(c)2006年爱思唯尔公司All rights reserved.
Ti-containing alpha-Keggin polyoxometalates (POMs) have been proved with properties of both anti-tumor and anti-HIV (human immunodeficiency virus). The potential anti-SARS (severe acute respiratory syndrome) activity of the POMs [alpha-PTi2W10O40](7-) isomers was investigated in this paper by molecular modeling method. The SARS 3c like protease, namely the SARS 3CL(pro) is the key function protease for virus replication as well as transcription and thus can be taken as one of the key targets for anti-SARS drug design. Affinity/Insight II was used to explore possible binding locations for POMs/3CL(pro) interaction. Charges in the POMs were obtained from density-functional theory (DFT) method. The results show that POMs bind with 3CL(pro) in the active site region with high affinity; POMs are more prone to bind with 3CL(pro) than with some organic compounds; for the POMs/3CL(pro) complex, the OTi2 in POMs is the vital element for electrostatic interaction, and the electrostatic binding energy is strong enough to keep the complex stable. (c) 2006 Elsevier Inc. All rights reserved.