Table 1. Potential Compound Binding Sites Identified Using Molecular Modeling of the CGRP Receptorb.
| site | FT map cluster ranking | centre of glide docking box | mean docking score | best docking score | best ligand | description |
|---|---|---|---|---|---|---|
| 1 | 0, 2, 6 | P97, Cβ | –4.50 | –5.24 | 3 | between peptide and ECL1, ECL2, P97R (ECD), and V111RAMP1 (ECD) |
| V111RAMP1, Cγ | –4.94 | –6.06 | 11 | |||
| 2 | 1, 5 | Y227, OH | N/A | deep within TM helix | ||
| 3 | 3 | D366, Oδ2 | –3.97 | –4.54 | 3 | between peptide and D366 (top of TM7) |
| 4 | 4 | W69, CH2 P97, Cβ V111RAMP1, Cγ2 | –4.76 | –6.55 | 11 | Near-CLR N-terminal helix, opposite side of ECD to CGRP C-terminus, there is overlap between the W69 and V111RAMP1sites. |
| 4a | W69, CH2 | –4.16 | –4.57 | 11 | as isolated ECD (3N7R)a | |
| 5 | 7 | R173, Cγ | –4.91 | –4.87 | 8 | G protein binding site |
| 6 | 8 | W72, Nε1 | –4.09 | –4.58 | 10 | adjacent to F37 of CGRP peptide, between CLR and RAMP1 |
| 7 | 9 | D90, Oδ1 | –5.24 | –6.20 | 10 | Between ECL1, the N-terminal end of the N-terminal helix, the C-terminal end of the peptide helix; overlaps the W69 site. |
| 8 | 10 | D90RAMP1, Oδ2 | –4.40 | –5.45 | 6 | top of ECD between CLR and RAMP1 |
| 9 | N/A | P343, Cβ | –4.32 | –5.45 | 6 | External face of TM7/TM7 |
| 10 | N/A | V304, Cγ1 | –4.50 | –5.03 | 11 | external face of TM5, adjacent to RAMP1 |
a
Site 4 when modeled as the isolated ECD (3N7R), which gave weaker docking scores. Sites close to the CLR:RAMP1 interface are described in italics.
b
Correspondence between the FTmap cluster and the center of the Glide docking boxes is shown. FTmap scores are ranked from highest (0) to lowest (10). N/A indicates sites were not identified by FTmap. Residue numbers indicate amino acids in CLR unless stated.