中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
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

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