Peptide ligand screening of alpha-synuclein aggregation modulators by in silico panning.
Peptide ligand screening of alpha-synuclein aggregation modulators by in silico panning.
复制标题
通过计算机淘选对 α-突触核蛋白聚集调节剂进行肽配体筛选。
DOI：
10.1186/1471-2105-8-451
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发表时间：
2007-11-16
影响因子：
3
通讯作者：
Ikebukuro, Kazunori
中科院分区：
文献类型：
--
作者：
Abe, Koichi;Kobayashi, Natsuki;Sode, Koji;Ikebukuro, Kazunori
α-突触核蛋白是一种帕金森病相关蛋白。它在体内形成聚集体，这些聚集体引起细胞毒性。聚集抑制剂有望降低α-突触核蛋白的细胞毒性，最近有报道称聚集促进剂可以降低α-突触核蛋白的细胞毒性。因此，淀粉样蛋白聚集调节配体有望作为治疗药物。我们采用先前提出的硅筛选方法筛选α-突触核蛋白肽配体。在这项研究中，我们选择了一个非常疏水的区域作为目标，即淀粉样蛋白核形成区域。由于该区域不能溶于水，因此很难对其肽配体进行体外筛选。我们使用遗传算法和对接模拟进行了6轮计算机规划。经过硅筛选后，我们通过体外实验对硅筛选的顶级肽进行了评价。这些肽能够与α-突触核蛋白结合。我们证明了通过硅筛选α-突触核蛋白结合肽是可能的。筛选的多肽与α-synuclein结合，从而影响α-synuclein的聚集。
α-Synuclein is a Parkinson's-disease-related protein. It forms aggregates in vivo, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines. We screened peptide ligands against α-synuclein by in silico panning, a method which we have proposed previously. In this study, we selected as the target a very hydrophobic region known as the amyloid-core-forming region. Since this region cannot be dissolved in water, it is difficult to carry out the in vitro screening of its peptide ligand. We carried out 6 rounds of in silico panning using a genetic algorithm and a docking simulation. After the in silico panning, we evaluated the top peptides screened in silico by in vitro assay. These peptides were capable of binding to α-synuclein. We demonstrated that it is possible to screen α-synuclein-binding peptides by in silico panning. The screened peptides bind to α-synuclein, thus affecting the aggregation of α-synuclein.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
3
作者：
Yagi, Yukiko;Terada, Kotaro;Noma, Takahisa;Ikebukuro, Kazunori;Sode, Koji
通讯作者：
Sode, Koji
影响因子：
14.9
作者：
Ikebukuro K;Okumura Y;Sumikura K;Karube I
通讯作者：
Karube I
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT