Membrane receptors couple signaling pathways using various mechanisms. G Protein-Coupled Receptors (GPCRs) represent the largest class of membrane proteins involved in signal transduction across the biological membranes. They are essential targets for cell signaling and are of great commercial interest to the pharmaceutical industry. Recent advances made in molecular biology and computational chemistry offer a range of simulation and multiscale modeling tools for the definition and analysis of protein-ligand, protein-protein, and protein-membrane interactions. The development of new techniques on statistical methods and free energy simulations help to predict novel optimal ligands, G protein specificity and oligomerization. The identification of the ligand-binding activation mechanisms and atomistic determinants as well as the interactions of intracellular binding partners that bind to GPCR targets in different coupling states will provide greater safety in human life. In this review, recent approaches and applications of multiscale simulations on GPCRs were highlighted.

中文翻译：

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GPCR的多尺度模拟的当前状态。

膜受体使用多种机制偶联信号传导途径。G蛋白偶联受体（GPCR）是参与跨生物膜信号转导的最大类膜蛋白。它们是细胞信号转导必不可少的靶标，对制药业具有重要的商业意义。分子生物学和计算化学领域的最新进展为定义和分析蛋白质-配体，蛋白质-蛋白质和蛋白质-膜相互作用提供了一系列模拟和多尺度建模工具。统计方法和自由能模拟新技术的发展有助于预测新的最佳配体，G蛋白特异性和寡聚化。配体结合激活机制和原子决定簇的鉴定以及以不同偶联状态结合GPCR靶标的细胞内结合配偶体的相互作用将为人类生命提供更大的安全性。在这篇综述中，重点介绍了在GPCR上进行多尺度模拟的最新方法和应用。