Selectivity of Neutral/Weakly Basic P1 Group Inhibitors of Thrombin and Trypsin by a Molecular Dynamics Study
文献类型：期刊论文
| 作者 | Wu, Emilia L.1; Han, KeLi1; Zhang, John Z. H.2,3 |
| 刊名 | chemistry-a european journal
 |
| 出版日期 | 2008 |
| 卷号 | 14期号:28页码:8704-8714 |
| 关键词 | molecular dynamics molecular mechanics selectivity thrombin trypsin |
| 英文摘要 | molecular dynamics (md) simulations followed by molecular mechanics generalized born surface area (mm-gbsa) analyses have been carried out to study the selectivity of two neutral and weakly basic p1 group inhibitors (177 and cda) to thrombin and trypsin. detailed binding free energies between these inhibitors and individual protein residues are calculated by using a per-residue basis decomposition method. the analysis of the detailed interaction energies provides in-sight on the protein-inhibitor-binding mechanism and helps to elucidate the basis for achieving selectivity through interpretation of the structural and energetic results from the simulations. the study shows that the dominant factor of selectivity for both inhibitors is van der waals energy, which suggests better shape complementarity and packing with thrombin. nonpolar solvation free energy and total entropy contribution are also in favor of selectivity, but the contributions are much smaller. binding mode and structural analysis show that 177 binds to thrombin and trypsin in a similar binding mode. in contrast, the cda binds to thrombin and trypsin in very different modes. |
| WOS标题词 | science & technology ; physical sciences |
| 类目[WOS] | chemistry, multidisciplinary |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | serine-protease inhibitors ; orally bioavailable series ; free-energy decomposition ; structure-based design ; binding free-energies ; human alpha-thrombin ; crystal-structure ; factor xa ; plasminogen-activator ; resp model |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000260035900033 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/140785]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China 2.Nanjing Univ, Inst Theoret & Computat Chem, Sch Chem & Chem Engn, Nanjing 210093, Peoples R China 3.NYU, Dept Chem, New York, NY 10003 USA |
| 推荐引用方式 GB/T 7714 | Wu, Emilia L.,Han, KeLi,Zhang, John Z. H.. Selectivity of Neutral/Weakly Basic P1 Group Inhibitors of Thrombin and Trypsin by a Molecular Dynamics Study[J]. chemistry-a european journal,2008,14(28):8704-8714. |
| APA | Wu, Emilia L.,Han, KeLi,&Zhang, John Z. H..(2008).Selectivity of Neutral/Weakly Basic P1 Group Inhibitors of Thrombin and Trypsin by a Molecular Dynamics Study.chemistry-a european journal,14(28),8704-8714. |
| MLA | Wu, Emilia L.,et al."Selectivity of Neutral/Weakly Basic P1 Group Inhibitors of Thrombin and Trypsin by a Molecular Dynamics Study".chemistry-a european journal 14.28(2008):8704-8714. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。