In Silico Design of a Peptide Receptor for Dopamine Recognition

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.     

表面等离子体共振传感器生物识别分子的固定化方法

表面等离子体共振具有无需标记样品和实时检测等优点,广泛应用于药物筛选以及生物、药物、食品等领域的检测。构建合适的生物传感界面是提高检测灵敏度和选择性的重要途径。该文介绍了利用化学偶联生物识别分子的非定向固定方法,以及利用化学键合或生物分子的特异性反应定向固定生物识别分子的方法,比较了两种固定方法的优缺点,并讨论了未来的发展趋势。