Docking and molecular dynamics studies of peripheral site ligand-oximes as reactivators of sarin-inhibited human acetylcholinesterase

被引：34

作者：

de Almeida, Joyce S. F. D. ^{[1
]}

Cuya Guizado, Teobaldo R. ^{[1
,2
]}

Guimaraes, Ana P. ^{[3
]}

Ramalho, Teodorico C. ^{[4
,7
]}

Goncalves, Arlan S. ^{[5
]}

de Koning, Martijn C. ^{[6
]}

Franca, Tanos C. C. ^{[1
,7
,8
]}

机构：

[1] Mil Inst Engn, Lab Mol Modeling Appl Chem & Biol Def LMACBD, Praca Gen Tiburcio 80, BR-22290270 Rio De Janeiro, Brazil

[2] Univ Estado Rio De Janeiro, Fac Technol, Rod Presidente Dutra Km 298, BR-27537000 Resende, RJ, Brazil

[3] Univ Fed Vicosa, Dept Chem, Ave Peter Henry Rolfs S-N,Campus Univ, Vicosa, MG, Brazil

[4] Univ Fed Lavras, Dept Chem, POB 3037, BR-37200000 Lavras, MG, Brazil

[5] Fed Inst Educ Sci & Technol, Ave Ministro Salgado Filho S-N, BR-29106010 Vila Velha, ES, Brazil

[6] TNO Def Secur & Safety, POB 45, NL-2280 AA Rijswijk, Netherlands

[7] Univ Hradec Kralove, Fac Informat & Management, Ctr Basic & Appl Res, Hradec Kralove, Czech Republic

[8] Concordia Univ, Dept Chem & Biochem, 7141 Sherbrooke W, Montreal, PQ, Canada

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2016年 / 34卷 / 12期

关键词：

acetylcholinesterase; nerve agents; peripheral site; oximes; reactivation; PROGRAM; MODEL;

D O I：

10.1080/07391102.2015.1124807

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.

引用

页码：2632 / 2642

页数：11

共 26 条

[1]

[Anonymous], 1999, PC SPARTAN PRO

[2] CHARMM - A PROGRAM FOR MACROMOLECULAR ENERGY, MINIMIZATION, AND DYNAMICS CALCULATIONS [J].