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磷酸二酯酶5与吴茱萸碱复合物的分子动力学模拟

Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine.

作者信息

Kobayashi Ayame, Nakajima Motokuni, Noguchi Yoh, Morikawa Ryota, Matsuo Yukiko, Takasu Masako

机构信息

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.

The Institute of Statistical Mathematics, Tokyo 190-8562, Japan.

出版信息

Life (Basel). 2023 Feb 18;13(2):578. doi: 10.3390/life13020578.

DOI:10.3390/life13020578
PMID:36836935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9968203/
Abstract

Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in , has inhibitory activity for PDE5. contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.

摘要

阿尔茨海默病是一种不可逆的神经疾病，目前尚无有效的小分子治疗药物。磷酸二酯酶5（PDE5）抑制剂是治疗阿尔茨海默病的候选药物。吴茱萸次碱是一种存在于[具体来源未提及]中的吲哚生物碱，对PDE5具有抑制活性。[具体来源未提及]中吴茱萸碱的含量高于吴茱萸次碱。因此，我们对PDE5与吴茱萸碱的复合物进行了分子动力学模拟。结果表明，与PDE5和（+）-吴茱萸碱复合物相比，PDE5与（-）-吴茱萸碱复合物位于反应中心内部。（-）-吴茱萸碱与PDE5的结合增加了PDE5的均方根偏差和回转半径。在含有（-）-吴茱萸碱复合物的PDE5中，被认为对活性很重要的M环的均方根波动值增加。这一结果表明（-）-吴茱萸碱可能具有抑制活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/49f4e97fb06f/life-13-00578-g014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/7674657db5a3/life-13-00578-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/afd9b65ae53b/life-13-00578-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/320757d312f8/life-13-00578-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/f4f62508d658/life-13-00578-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/49f4e97fb06f/life-13-00578-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/652169b5a444/life-13-00578-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/2e2bb9bfb43c/life-13-00578-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/cdadd8598bbe/life-13-00578-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/8934cc9edf70/life-13-00578-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/5e546403b25a/life-13-00578-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/c00621c4247e/life-13-00578-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/8aef571fe067/life-13-00578-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/7674657db5a3/life-13-00578-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/afd9b65ae53b/life-13-00578-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/f127e45d9262/life-13-00578-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/320757d312f8/life-13-00578-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/ac7ad806b761/life-13-00578-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/f4f62508d658/life-13-00578-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29a1/9968203/49f4e97fb06f/life-13-00578-g014.jpg

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