Computational studies of acetylcholinesterase complexed with fullerene derivatives: a new insight for Alzheimer disease treatment

被引:21
作者
Goncalves, Arlan da Silva [1 ]
Costa Franca, Tanos Celmar [2 ,3 ]
de Oliveira, Osmair Vital [1 ]
机构
[1] Fed Inst Educ Sci & Technol Espirito Santo, Unit Vila Velha, Ave Minist Salgado Filho 1000, BR-29106010 Soteco, ES, Brazil
[2] Mil Inst Engn, Lab Mol Modeling Appl Chem & Biol Def LMCBD, Rio De Janeiro, RJ, Brazil
[3] Univ Hradec Kralove, Ctr Basic & Appl Res, Fac Informat & Management, Hradec Kralove, Czech Republic
关键词
fullerene derivatives; Alzheimer's disease; theoretical methodologies; AChE inhibition; docking; molecular modeling; MOLECULAR-DYNAMICS SIMULATIONS; MECHANISMS; ELECTROSTATICS; REACTIVATORS; ANTIOXIDANTS; INHIBITION; DOCKING; GROMACS; DESIGN; 2-PAM;
D O I
10.1080/07391102.2015.1077345
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
Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer's disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72, Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the drug design of new inhibitors of HssAChE based on C60 derivatives. Results presented here report for the first time by a new class of molecules that can become effective drugs against AD.
引用
收藏
页码:1307 / 1316
页数:10
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