In silico design of BACE1 inhibitor for Alzheimer's disease by traditional Chinese medicine.
In silico design of BACE1 inhibitor for Alzheimer's disease by traditional Chinese medicine.
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DOI：
10.1155/2014/741703
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发表时间：
2014
影响因子：
--
通讯作者：
Chen CY
中科院分区：
文献类型：
--
作者：
Huang HJ;Lee CC;Chen CY
β-淀粉样前体蛋白裂解酶1（β-site APP cleaving enzyme 1，BACE 1）是导致阿尔茨海默病（Alzheimer's disease，AD）的重要靶点，由于脑内沉积的β淀粉样肽（Aβ）需要BACE 1和γ-分泌酶裂解淀粉样前体蛋白（amyloid precursor protein，APP），但目前AD的治疗仍存在副作用。本研究利用世界上最大的中药数据库和数据库筛选，提供潜在的BACE 1抑制化合物。采用分子动力学模拟方法观察了配体结合后的动力学结构。我们发现雷公藤甲素B1的毒性比嘧啶类似物小，嘧啶类似物与BACE 1的结合亲和力更强。对于轨迹分析，在5000 ps的模拟时间内，所有构象都趋于稳定。在动态蛋白质验证中，结合区的残基在分子动力学模拟后仍然是稳定的。通过快照比较，我们发现Triptofordin B1可以减少BACE 1的结合空腔，结果表明Triptofordin B1可以与BACE 1结合，并且比对照更好，这可以作为潜在的先导药物设计新型BACE 1抑制剂用于AD治疗。
The β-site APP cleaving enzyme 1 (BACE1) is an important target for causing Alzheimer's disease (AD), due to the brain deposition peptide amyloid beta (Aβ) require cleavages of amyloid precursor protein (APP) by BACE1 and γ-secretase, but treatments of AD still have side effect in recent therapy. This study utilizes the world largest traditional Chinese medicine (TCM) database and database screening to provide potential BACE1 inhibited compound. Molecular dynamics (MD) simulation was carried out to observe the dynamics structure after ligand binding. We found that Triptofordin B1 has less toxicity than pyrimidine analogue, which has more potent binding affinity with BACE1. For trajectory analysis, all conformations are tending to be stable during 5000 ps simulation time. In dynamic protein validation, the residues of binding region are still stable after MD simulation. For snapshot comparison, we found that Triptofordin B1 could reduce the binding cavity; the results reveal that Triptofordin B1 could bind to BACE1 and better than control, which could be used as potential lead drug to design novel BACE1 inhibitor for AD therapy.
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DOI：
10.1080/07391102.2009.10507315
发表时间：
2009-12-01
影响因子：
4.4
作者：
Chen, Calvin Yu-Chian
通讯作者：
Chen, Calvin Yu-Chian
影响因子：
4.4
作者：
Chen, Kuan-Chung;Chang, Su-Sen;Chen, Calvin Yu-Chian
通讯作者：
Chen, Calvin Yu-Chian
影响因子：
3.7
作者：
Chen, Kuan-Yu;Chang, Su-Sen;Chen, Calvin Yu-Chian
通讯作者：
Chen, Calvin Yu-Chian
影响因子：
2.9
作者：
Chen, Calvin Yu-Chian
通讯作者：
Chen, Calvin Yu-Chian
影响因子：
4.8
作者：
Grimm MO;Mett J;Stahlmann CP;Haupenthal VJ;Zimmer VC;Hartmann T
通讯作者：
Hartmann T