A study on innovative computer simulation for drug design

药物设计创新计算机模拟研究

• 批准号: 11695096
• 负责人: AKAHO Eiichi
• 金额: $ 1.41万
• 依托单位: Kobe Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11695096/
• 关键词: computer simulation; drug design; docking; receptor; enzyme inhibitor; computational chemistry; drug development; hydrogen boding; 酵素; 阻害物質; コンピュータ・ドッキング; コンピュータ・モデリング; 結合様式

It is reported that non-steroidal anti-inflammatory drugs that block COX2 without inhibiting COX1 will be a better compound with less side effects. A proposal has been made to simulate enzyme selectivity by using Dcok4.0 and an article has been published in J.Chem. Software, 5(4) 147-62, (1999). Derivatives of HIV protease inhibitors have been synthesized by taking into consideration the structure of ligand complexes in HIV protease and a comparative study has been made between their Ki values and the Gibb's free energy obtained by applying molecular interaction between the enzyme and the ligand. A fair correlation was obtained and an article was reported in J.Chem. Software, 7(3) 103-114, (2001).Derivatives of anti-inflammatory agents with indole skeleton have been synthesized and their COX2 selectivity was examined by applying the originally proposed method and the paper was submitted to European Journal of Medicinal Chemistry.Docking modes of anti-inflammatory sampangine against DNA was investigated and we are in preparation to submit the result for publication. Besides, Docking modes of tyrosine kinase inhibitors and COX2 selective compounds retrieved from chemical substance database have been investigated, and the results will be published.Quite a few numbers of three-dimensional structures of prote in and DNA have been discovered and will be discovered more and more in the future . In addition to this feature, computer technology has made an enormous advancement. By applying these two types of advanced knowledge, we will continue to conduct docking research

据报道，阻断COX 2而不抑制COX 1的非甾体抗炎药将是副作用更小的更好化合物。已经提出了通过使用Dcok4.0来模拟酶选择性的建议，并且已经在J. Chem. Software，5（4）147-62，（1999）中发表了一篇文章。通过考虑HIV蛋白酶中配体配合物的结构，合成了HIV蛋白酶抑制剂的衍生物，并比较研究了它们的Ki值与通过应用酶与配体之间的分子相互作用获得的Gibb自由能之间的关系。获得了一个公平的相关性，并且在J. Chem. Software，7（3）103-114中报道了一篇文章，（2001）。已经合成了具有吲哚骨架的抗炎剂的衍生物，并且通过应用最初提出的方法检测了它们的C 0X 2选择性，并且该论文被提交给欧洲医学化学杂志。我们研究了炎症性桑潘金对DNA的作用，并准备提交结果供发表。此外，还对酪氨酸激酶抑制剂和COX 2选择性化合物的对接模式进行了研究，并将结果发表，发现了相当数量的蛋白质和DNA的三维结构，今后还会发现更多的蛋白质和DNA的三维结构。除此之外，计算机技术也取得了巨大的进步。通过应用这两类先进知识，不断进行对接研究

项目成果

E.Akaho,C.Fujikawa,H.I.Runion,C.R.Hill,and H.Nakano: "A Study on Binding Modes of Nonsteroidal Antiinflammatory Drugs to Cox1 and Cox2 as Obtained by Dock4.0"The Journal of Chemical Software. 5・4. 147-162 (1999)

E. Akaho、C. Fujikawa、H. I. Runion、C. R. Hill 和 H. Nakano：“通过 Dock4.0 获得的非甾体抗炎药与 Cox1 和 Cox2 的结合模式的研究”化学软件杂志 5・4。 147-162 (1999)

Eiichi AKAHO: "A study on binding modes of non-steroidal anti-inflamm-atory drugs to COX1 and COX2 as obtained by Dock4.0"J.Chem.Software. 5. 147-162 (1999)

Eiichi AKAHO：“通过 Dock4.0 获得的非甾体抗炎药与 COX1 和 COX2 结合模式的研究”J.Chem.Software。

Eiichi AKAHO: "A study on docking mode of HIV protease and their inhibitors"J.Chem.Software. 7. 103-114 (2001)

Eiichi AKAHO：“HIV蛋白酶及其抑制剂的对接模式研究”J.Chem.Software。

Eiichi AKAHO, et al.: "A study on binding modes of non-steroidal anti-Inflammatory drugs to COX1 and COX2 as obtained by Dcok4.0"J.Chem.Software. 5(4). 147-162 (1999)

Eiichi AKAHO 等人：“通过 Dcok4.0 获得的非甾体抗炎药与 COX1 和 COX2 结合模式的研究”J.Chem.Software。

Eiichi AKAHO: "A study on docking mode of HIV protease and their inhibitors"J.Chem.Software. 5(4). 103-114 (2001)

Eiichi AKAHO：“HIV蛋白酶及其抑制剂的对接模式研究”J.Chem.Software。