Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH
文献类型：期刊论文
| 作者 | Luo, Hua-Jun2; Wang, Jun-Zhi2; Huang, Nian-Yu2; Deng, Wei-Qiao1,2; Zou, Kun2 |
| 刊名 | JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
 |
| 出版日期 | 2016 |
| 卷号 | 30期号:1页码:27-37 |
| 关键词 | Potassium-competitive Acid Blockers Induced-fit Docking Binding Free Energy Protonated Form H++ k+-atpase |
| ISSN号 | 0920-654X |
| DOI | 10.1007/s10822-015-9886-8 |
| 文献子类 | Article |
| 英文摘要 | The interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives (compound 1 (N, N-Dipropyl-1-(2-phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-1H-1,2,3-triazole-4-methanamine) and 2 (1-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-4-(morpholin-4-ylmethyl)-1H-1,2,3-triazole)) with H+,K+-ATPase at different pH were studied by induced-fit docking, QM/MM optimization and MM/GBSA binding free energy calculations of two forms (neutral and protonated form) of compounds. The inhibition activity of compound 1 is measured and almost unchanged at different pH, while the activity of compound 2 increases significantly with pH value decreased. This phenomenon could be explained by their protonated form percentages and the calculated binding free energies of protonated and neutral mixture of compounds at different pH. The binding free energy of protonated form is higher than that of neutral form of compound, and the protonated form could be a powerful inhibitor of H+,K+-ATPase. By the decomposed energy comparisons of residues in binding sites, Asp137 should be the key binding site to protonated form of compound because of the hydrogen bond and electrostatic interactions. These calculation results could help for further rational design of novel H+,K+-ATPase inhibitors. |
| WOS关键词 | K+-COMPETITIVE INHIBITOR ; PROTON PUMP INHIBITORS ; INDUCED-FIT DOCKING ; GASTRIC H,K ATPASE ; BINDING-SITES ; MUTATIONAL ANALYSIS ; H+/K+-ATPASE ; DRUG TARGET ; H,K-ATPASE ; VESICLES |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000367595200003 |
| 出版者 | SPRINGER |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/171462]  |
| 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 |
| 通讯作者 | Luo, Hua-Jun |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian, Peoples R China 2.China Three Gorges Univ, Coll Biol & Pharmaceut Sci, Hubei Key Lab Nat Prod Res & Dev, Yichang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Hua-Jun,Wang, Jun-Zhi,Huang, Nian-Yu,et al. Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,2016,30(1):27-37. |
| APA | Luo, Hua-Jun,Wang, Jun-Zhi,Huang, Nian-Yu,Deng, Wei-Qiao,&Zou, Kun.(2016).Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH.JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,30(1),27-37. |
| MLA | Luo, Hua-Jun,et al."Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH".JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN 30.1(2016):27-37. |
入库方式： OAI收割
来源：大连化学物理研究所
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