Department of Physics, Tampere University of Technology, Finland.
J Neurochem. 2012 Aug;122(4):681-90. doi: 10.1111/j.1471-4159.2012.07813.x. Epub 2012 Jun 27.
The interactions of the neurotransmitter dopamine, and its precursor l-dopa, with membrane lipids were investigated through a set of molecular dynamic simulations with all atom resolution. The results obtained indicate that both dopamine and l-dopa have a pronounced association with the lipid head groups, predominantly mediated through H-bonds. As a result the molecules are anchored to the interfacial region of the membrane. The strength of this interaction is dependent on lipid composition - the presence of phosphatidylserine leads to an increase in the strength of this interaction, resulting in an H-bond network with a lifetime much longer than the timescale of our simulations. Also, bilayers that include sphingomieline and cholesterol interact strongly with dopamine and l-dopa. We postulate that the high membrane association that we have observed for both dopamine and l-dopa could have the following effects: 1) when on the plasma membrane exterior, favour the availability of these compounds for cell membrane uptake processes and, 2) when on an internal membrane surface, accentuate the importance of membrane-bound metabolizing enzymes over their soluble counterparts.
通过一系列具有全原子分辨率的分子动力学模拟，研究了神经递质多巴胺及其前体左旋多巴与膜脂的相互作用。结果表明，多巴胺和左旋多巴都与脂质头部基团有明显的相互作用，主要通过氢键介导。因此，这些分子被锚定在膜的界面区域。这种相互作用的强度取决于脂质组成-磷脂酰丝氨酸的存在会增加这种相互作用的强度，导致氢键网络的寿命比我们模拟的时间尺度长得多。此外，含有鞘氨醇和胆固醇的双层膜与多巴胺和左旋多巴强烈相互作用。我们推测，我们观察到的多巴胺和左旋多巴在膜上的高亲和力可能有以下影响：1）当在质膜外侧时，有利于这些化合物可用于细胞膜摄取过程，2）当在内部膜表面时，强调膜结合代谢酶相对于其可溶性对应物的重要性。
