The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study

	The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study
	Yang, Zhiwei 1; Yang, Gang 1; Zu, Yuangang 1; Fu, Yujie 1; Zhou, Lijun 1,2
刊名	physical chemistry chemical physics
	2009
卷号	11 期号:43 页码:10035-10041
英文摘要	with the aid of density functional calculations, it was revealed that neuraminidase (na) inhibitors (scheme 1) exist exclusively in the neutral form. however, the docking and molecular dynamics simulations indicated that the zwitterionic, rather than neutral, isomers are the active form in na-receptors. the neutral and zwitterionic isomers of ba (compound 7 in scheme 1) are quite different in structure and is therefore expected to show distinct bioactivities. with the addition of four water molecules, the geometry of the neutral isomer (nba4) is induced to resemble the zwitterion and remains rather stable throughout the proton transfer process (nba4 -> zba4); in addition, the energy difference between the zwitterionic vs. the neutral isomer is lowered from 24.76 to 2.54 kcal mol(-1). the zwitterion is the predominant isomer in aqueous solution, consistent with the conformational preference in na-receptors. the proton transfer process of nba4 -> zba4 is divided into two elementary steps. step 1, rather than step 2, plays a decisive role, owing to the larger energy barrier; however, step 1 is not assisted by solvent water, even if it is not water-suppressed. accordingly, the proton transfer process that leads to the formation of zwitterions is not facilitated in aqueous solution, albeit they may be more stable than the neutral isomers. it is thus suggested that the designed antiviral inhibitors should be facile to transform into the zwitterionic form in aqueous solution. in this way, the oral bioavailability of the antiviral drugs can be improved.
WOS标题词	science & technology ; physical sciences
类目[WOS]	chemistry, physical ; physics, atomic, molecular & chemical
研究领域[WOS]	chemistry ; physics
关键词[WOS]	influenza-virus neuraminidase ; density-functional theory ; amino-acid zwitterions ; free-energy ; molecular-dynamics ; water clusters ; drug design ; binding ; potent ; sensitivity
收录类别	SCI
语种	英语
WOS记录号	WOS:000271243400011
公开日期	2015-11-17
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/141319]
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.NE Forestry Univ, Minist Educ, Key Lab Forest Plant Ecol, Harbin 150040, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Yang, Zhiwei,Yang, Gang,Zu, Yuangang,et al. The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study[J]. physical chemistry chemical physics,2009,11(43):10035-10041.
APA	Yang, Zhiwei,Yang, Gang,Zu, Yuangang,Fu, Yujie,&Zhou, Lijun.(2009).The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study.physical chemistry chemical physics,11(43),10035-10041.
MLA	Yang, Zhiwei,et al."The conformational analysis and proton transfer of neuraminidase inhibitors: a theoretical study".physical chemistry chemical physics 11.43(2009):10035-10041.