Predicted structural changes and molecular dynamic modeling of wild-type and mutant hCLR and hCLR:RAMP2 complexes. (A and B) Predicted structural conformations of the hCLR and hCLR(V205del) by homology modeling using SWISS-MODEL. Cartoon views of the receptors predict structural changes centered on the site of mutation in extra cellular loop 1 (green). Inset shows predicted interactions involving side-chains and key residues are labeled to highlight changes in hydrogen bonding (H194/194, N200/200, N201/201, Q216/215, Y278/277, and S285/284), large residue positional changes (T196), and the site of deletion (V205 and A205). (C and D) Snap-shots of CLR–RAMP2–AM complexes after replica Monte Carlo simulations with either wild-type (C) or V205del (D) CLR. (E) Overlay of the RAMP/ECL1 interface of wild-type CLR–RAMP2–AM (blue) and CLR(V205del)–RAMP2–AM (red) complexes after REMC simulations. (F) Changes in root mean square deviation (RSMD) of wild-type and V205del CLR in complex with both RAMP1 and CGRP or RAMP2 and AM during REMC simulations.