Young Researchers and Elite Club, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Isfahan Cardiovascular Research Center, Isfahan cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Bioimpacts. 2013;3(4):177-83. doi: 10.5681/bi.2013.022. Epub 2013 Jul 17.
M3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. We proposed that antagonists of the M3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development.
Comparative modeling and fold recognition algorithms have been used for prediction of M3 protein 3-D model. Evaluation of the models using Q-mean and ProSA-web score, has led to choosing predicted model by fold recognition algorithm as the best model which was minimized regarding energy level using Molegro Virtual Docker 2011.4.3.0 (MVD) software. Pockets and active sites of model were recognized using MVD cavity detection, and MetaPocket algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD was used for computer simulated docking study; MolDock SE was selected as docking scoring function and final results were evaluated based on MolDock and Re-rank score.
Docking data suggested that prilocaine, which is generally applied as a topical anesthetic, binds strongly to 3-D model of M3 protein.
This study proposes that prilocaine is a potential inhibitor of M3 protein and possibly has immune enhancing properties.
M3 蛋白是一种趋化因子诱饵受体，参与γ疱疹病毒的持续感染发病机制以及与该病原体潜伏期相关的并发症。我们提出，M3 的拮抗剂将为研究免疫系统紊乱、免疫缺陷状态以及趋化因子在发病机制发展中的作用的新治疗策略提供独特的机会。
使用比较建模和折叠识别算法预测 M3 蛋白的 3D 模型。使用 Q-mean 和 ProSA-web 评分评估模型，选择折叠识别算法预测的模型作为最佳模型，然后使用 Molegro Virtual Docker 2011.4.3.0（MVD）软件根据能量水平对其进行最小化。使用 MVD 腔探测和 MetaPocket 算法识别模型的口袋和活性部位。筛选 KEGG 数据库中可用的一万种化合物；使用 MVD 进行计算机模拟对接研究；选择 MolDock SE 作为对接评分函数，并根据 MolDock 和重新排序评分评估最终结果。
对接数据表明，普鲁卡因通常用作局部麻醉剂，与 M3 蛋白的 3D 模型结合紧密。
本研究表明，普鲁卡因可能是 M3 蛋白的潜在抑制剂，并且具有增强免疫的特性。
