分子动力学模拟:神经元钙传感蛋白生理机制研究的新方向

Molecular dynamics simulation:a new direction targeting physiological mechanisms of neuronal calcium sensor-1 protein

背景:神经元钙传感蛋白的生理功能及其发挥、结构折叠与解折叠的研究多采用实验方法进行研究,并提出蛋白可能的作用机制模型及维持结构稳定的可能因素,但实验手段受到时间和空间分辨的局限以及蛋白结构的复杂性,研究受到一定的限制,导致实验中提出的很多理论模型无法得以检验。分子动力学能够从原子水平上观察并解释实验现象,对理论假设和(或)模型进行验证,为实验提供参考和启示;也可以预测新的结构和现象,为建立理论模型和作用机制提供依据。目的:分别对采用实验方法和分子动力学模拟的方法对神经元钙传感蛋白生理功能及其机制研究的进展进行梳理,并对今后的研究做一展望。方法:以"Neuronal Calcium Sensor-1 or Neuronal Calcium Sensor1 or Neuronal Calcium Sensor 1 or NCS-1"为主题词,检索Pub Med数据库中有关神经元钙传感蛋白研究的相关文献,下载全文进行阅读,排除与蛋白生理机制无关的文章,最终对72篇文献进行归纳总结。结果与结论:(1)实验中主要对神经元钙传感蛋白在不同条件、不同位置中调控分泌、调控多巴胺D2受体、在肝细胞内调控腺苷A2A受体以及调控不同刺激下心肌细胞质和细胞核Ca^(2+)等方面提出相关理论模型;(2)分子动力学模拟从结构的视角,对维持蛋白结构稳定的关键因素进行了分析和总结;(3)建议将两种方法结合起来,不断加深对蛋白生理机制的理解,共同推动研究的深入发展。

BACKGROUND： Physiological functions, structural fold and unfolding of neuronal calcium sensor-1（NCS-1） have been explored in a series of experiments, and then the possible mechanism models and key factors forremaining the structural stability are raised. But many functional models cannot be verified due to the limitations of resolution of the time and space and complex protein structure. The experimental phenomena and hypothesis or models may be tested at the atom levels by molecular dynamics, and the new structure may be predicted to provide basis for model establishment and functional mechanisms. OBJECTIVE： To overview the research process of physiological functions and mechanisms of NCS-1 using the experimental method and molecular dynamics simulations, thereby providing basis for future research. METHODS： Pub Med database was retrieved for the literatures addressing NCS-1 using the English subject term ＂Neuronal Calcium Sensor-1 or Neuronal Calcium Sensor1 or Neuronal Calcium Sensor 1 or NCS-1＂. Finally, 72 articles were included in result analysis based on the inclusion and exclusion criteria. RESULTS AND CONCLUSION： The theoretical models of NCS-1 in secretion regulation, dopamine D2 receptor regulation, adenosine A2 A receptor regulation in hepatocytes and Ca-（2＋） regulation in myocardial cytoplasm and nuclei with different stimuli are put forward. The key factors to remaining structural stability are analyzed and summarized by modular dynamics simulation in view of structure. It is recommended to combine these two methods in order to deeply understand the protein functional mechanisms, thereby pushing the in-depth study.