%0 Journal Article
%A Alfonso-Prieto, Mercedes
%A Giorgetti, Alejandro
%A Carloni, Paolo
%T Multiscale simulations on human Frizzled and Taste2 GPCRs
%J Current opinion in structural biology
%V 55
%@ 0959-440X
%C Amsterdam [u.a.]
%I Elsevier
%M FZJ-2019-02680
%P 8-16
%D 2019
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30933747
%U <Go to ISI:>//WOS:000482514400004
%R 10.1016/j.sbi.2019.02.009
%U https://juser.fz-juelich.de/record/862342