Dopamine (DA) is an important neurotransmitter with a fundamental role in regulatory functions related to the central, peripheral, renal, and hormonal nervous systems. Dopaminergic neurotransmission dysfunctions are commonly associated with several diseases; thus, in situ quantification of DA is a major challenge. To achieve this goal, enzyme-based biosensors have been employed for substrate recognition in the past. However, due to their sensitivity to changes in temperature and pH levels, new peptide bioreceptors have been developed. Therefore, in this study, four bioreceptors were designed in silico to exhibit a higher affinity for DA than the DA transporters (DATs). The design was based on the hot spots of the active sites of crystallized enzyme structures that are physiologically related to DA. The affinities between the chosen targets and designed bioreceptors were calculated using AutoDock Vina. Additionally, the binding free energy, ∆G, of the dopamine-4xp1 complex was calculated by molecular dynamics (MD). This value presented a direct relationship with the E_refine value obtained from molecular docking based on the ∆G functions obtained from MOE of the promising bioreceptors. The control variables in the design were amino acids, bond type, steric volume, stereochemistry, affinity, and interaction distances. As part of the results, three out of the four bioreceptor candidates presented promising values in terms of DA affinity and distance.

中文翻译：

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用于多巴胺识别的肽受体的计算机设计


多巴胺 (DA) 是一种重要的神经递质，在中枢、外周、肾脏和激素神经系统相关的调节功能中发挥着重要作用。多巴胺能神经传递功能障碍通常与多种疾病相关。因此，DA的原位定量是一个重大挑战。为了实现这一目标，过去已采用基于酶的生物传感器进行底物识别。然而，由于它们对温度和 pH 水平变化的敏感性，新的肽生物受体已经被开发出来。因此，在本研究中，通过计算机设计了四种生物受体，以比 DA 转运蛋白 (DAT) 表现出更高的 DA 亲和力。该设计基于与 DA 生理相关的结晶酶结构活性位点的热点。使用 AutoDock Vina 计算所选目标和设计的生物受体之间的亲和力。此外，多巴胺-4xp1 复合物的结合自由能 ΔG 是通过分子动力学 (MD) 计算的。该值与基于从有前景的生物受体的 MOE 获得的 ΔG 函数的分子对接获得的 E_refine 值存在直接关系。设计中的控制变量是氨基酸、键类型、空间体积、立体化学、亲和力和相互作用距离。作为结果的一部分，四种候选生物受体中的三种在 DA 亲和力和距离方面呈现出有希望的值。