Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH

doi:10.1007/s10822-015-9886-8

	Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH
	Luo, Hua-Jun 2; Wang, Jun-Zhi 2; Huang, Nian-Yu 2; Deng, Wei-Qiao 1,2; Zou, Kun 2
刊名	JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
	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
出版者	SPRINGER
WOS记录号	WOS:000367595200003
内容类型	期刊论文
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.