Study of the translocation mechanism of octopamine in the dopamine transporter. New insights from molecular simulation studies.

A. Fierro, S. Arancibia
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Abstract

A different monoaminergic system (MS) of fundamental importance in invertebrates compared with mammals is the octopaminergic system, which exerts and regulates different central and peripheral processes by specific receptors and transporters. Despite the abundant information available on the functions of octopamine and their receptors in insect physiology, differences associated at octopamine re-uptake process in this neural system remain unexplored. Using AutoDock 4.0 (1) dopamine (DA) and octopamine (OA) were evaluated in the crystal structure of Drosophila melanogaster DAT (PDBid: 4XP1). The complex DAT/ligand was inserted into a POPC membrane, solvating with water model TIP3. The PBC and NPT ensemble was used to perform MD calculations for 20 ns using NAMD 2.6 (2). Finally steered molecular dynamics simulations fixed the center of mass of the ligands and a constant velocity protocol was employed, with a pulling velocity of 0.0001 A/timestep, for 40 ns and SMD spring constant to each system was 4 Kcal/mol/A2. Thus, force profile determination to DA and OA crossing DAT were obtained using steered molecular dynamics simulations. Our computational results show a similar profile to both substrates in DAT. References. (1) Autodock: G. Morris, R. Huey, A. Olson, Using AutoDock for ligand-receptor docking. Current Protocols in Bioinformatics, (2008) chapter 8 Unit 8.14. (2) NAMD: J. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. Skeel, L. Kale, K. Schulten, Scalable molecular dynamics with NAMD. Journal of Computational Chemestry, (2005) 26 1781–1802.
章鱼胺在多巴胺转运体中的转运机制研究。分子模拟研究的新见解。
与哺乳动物相比,无脊椎动物的另一个重要单胺系统是章鱼胺系统,它通过特定的受体和转运体发挥和调节不同的中枢和外周过程。尽管关于章鱼胺及其受体在昆虫生理学中的功能有丰富的信息,但与章鱼胺再摄取过程相关的神经系统差异仍未被探索。利用AutoDock 4.0(1)对黑胃果蝇DAT (PDBid: 4XP1)晶体结构中的多巴胺(DA)和章鱼胺(OA)进行了评价。将复合物DAT/配体插入POPC膜中,用水模型TIP3溶剂化。采用NAMD 2.6(2),利用PBC和NPT集成进行20 ns的MD计算。最后,定向分子动力学模拟固定配体的质心,采用等速方案,拉速为0.0001 a /时间步长,拉速为40 ns,每个体系的SMD弹簧常数为4 Kcal/mol/A2。因此,利用定向分子动力学模拟获得了DA和OA穿过DAT的力分布确定。我们的计算结果显示了相似的轮廓,这两种底物在DAT。参考文献(1) Autodock技术在配体与受体对接中的应用。当前生物信息学协议,(2008)第8章第8.14单元。(2) NAMD: J. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. Skeel, L. Kale, K. Schulten。计算化学学报,(2005)26 1781-1802。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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