Recently, molecular dynamics simulations, from all atom and coarse grained to hybrid methods bridging the two scales, have provided exciting functional insights into class F (Frizzled and Taste2) GPCRs (about 40 members in humans). Findings include: (i) The activation of one member of the Frizzled receptors (FZD4) involves a bending of transmembrane helix TM7 far larger than that in class A GPCRs. (ii) The affinity of an anticancer drug targeting another member (Smoothened receptor) decreases in a specific drug-resistant variant, because the mutation ultimately disrupts the binding cavity and affects TM6. (iii) A novel two-state recognition mechanism explains the very large agonist diversity for at least one member of the Taste2 GPCRs, hTAS2R46.

中文翻译：

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对人类毛躁和Taste2 GPCR的多尺度模拟。

最近，分子动力学模拟，从所有原子和粗粒度的方法到桥接这两个尺度的混合方法，已经为F类（Frizzled和Taste2）GPCR（人类中约40个成员）提供了令人兴奋的功能见解。研究结果包括：（i）卷曲蛋白受体（FZD4）的一个成员的激活涉及跨膜螺旋TM7的弯曲，其弯曲程度远大于A类GPCR中的弯曲。（ii）在特定的药物抗性变异体中，靶向另一成员的抗癌药物的亲和力降低，因为该突变最终破坏了结合腔并影响了TM6。（iii）一种新颖的两种状态识别机制解释了至少一种Taste2 GPCRs hTAS2R46成员具有非常大的激动剂多样性。