Setiadi Jeffry, Heinzelmann Germano, Kuyucak Serdar
School of Physics, University of Sydney, New South Wales, Sydney 2006, Australia.
Departamento de Fisica, Universidade Federal de Santa Catarina, Florianopolis 88040-900, Santa Catarina, Brazil.
Biomolecules. 2015 Nov 11;5(4):3067-86. doi: 10.3390/biom5043067.
Glutamate is the major excitatory neurotransmitter in the human brain whose binding to receptors on neurons excites them while excess glutamate are removed from synapses via transporter proteins. Determination of the crystal structures of bacterial aspartate transporters has paved the way for computational investigation of their function and dynamics at the molecular level. Here, we review molecular dynamics and free energy calculation methods used in these computational studies and discuss the recent applications to glutamate transporters. The focus of the review is on the insights gained on the transport mechanism through computational methods, which otherwise is not directly accessible by experimental probes. Recent efforts to model the mammalian glutamate and other amino acid transporters, whose crystal structures have not been solved yet, are included in the review.
谷氨酸是人类大脑中的主要兴奋性神经递质，它与神经元上的受体结合会使神经元兴奋，而多余的谷氨酸则通过转运蛋白从突触中清除。细菌天冬氨酸转运体晶体结构的确定为在分子水平上对其功能和动力学进行计算研究铺平了道路。在这里，我们回顾了这些计算研究中使用的分子动力学和自由能计算方法，并讨论了它们最近在谷氨酸转运体上的应用。综述的重点是通过计算方法获得的关于转运机制的见解，而这些见解是实验探针无法直接获得的。综述还包括了对尚未解析晶体结构的哺乳动物谷氨酸和其他氨基酸转运体进行建模的最新努力。
