TABLE 1

Major constraints used in Modeler

GLP-1R Position (A)	GLP-1 Position (B)	Origin for GLP-1R – GLP-1 Constraint	Constraint^a (Å)	Reference
ECD; E133; C_γ	A24; C_β	Bpa²⁴ GLP-1 photoaffinity crosslink.	r_AB ≤ 9.0	Chen et al. 2009^c
TM1; L141;C_δ₁	V16; C_γ₁	Bpa¹⁶ GLP-1 photoaffinity crosslink.	r_AB ≤ 9.0	Miller et al. (2011)
TM1; Y145;C_ξ	F12; C_γ	Bpa¹² GLP-1 photoaffinity crosslink.	r_AB ≤ 6.0	Chen et al. (2010)
ECL2; W297;C_η₂	L20; C_γ	Bpa²⁰ GLP-1 photoaffinity crosslink.	r_AB ≤ 9.0	Miller et al. (2011)
TM2; K197;N_ξ	E9; O_ε₂	Reciprocal mutagenesis of residues between VIP and VIP-R-1/VIP-R-2 resulting in gain of function^b	r_AB ≤ 4.0	Solano et al. (2001); Vertongen et al. (2001)
ECL3; R380;N_η₂	D15; O_ε₂	Reciprocal mutagenesis of residues between GLP-1 and GLP-1R resulting in gain of function.	r_AB ≤ 4.0	Moon et al. (2015)

↵^a These distance constraints were estimated from preliminary models that used tyrosine to represent Bpa, since the O_η of the tyrosine is topologically equivalent to the reactive carbon atom of Bpa; a 6-Å constraint was used between the O_η and a suitable point on the target residue.
↵^b These residues are conserved between GLP-1R and VPAC-2R. The restraint gives similar results for E⁹ with K197 and/or R190; if the constraint is used with both residues it can be relaxed to r_AB ≤ 5.0 Å or r_AB ≤ 6.0 Å.
↵^c The potential constraint between O_ε₁ of E125 and C_α of G³⁵ reported by Chen et al. (2009) (21.5 Å) was not used as the distance in the ECD X-ray structure; this is possibly a constraint to another molecule within an oligomeric array.