BoltzMaker Report | Marc C. Deller

Campaign summary

Field	Value	Details
Input file	boltz_input.md	boltz_input.md
Proteins	2	4 protein block(s) in 2 group(s): GLP1R (463 aa); GIPR (466 aa); GLPAP (463 aa); GIPAP (466 aa)
Co-folded partners	3	GNAS (protein, 394 aa); GNB1 (protein, 340 aa); GNG2 (protein, 71 aa)
Ligands	3	ORFO (SMILES); LSN1 (SMILES); LSN2 (SMILES)
Pockets	2	41Y, V6G
Apo structure references	2	GLPAP, GIPAP
Predictions	20	GLP1R_ORFO, GLP1R_ORFO_41Y, GLP1R_ORFO_V6G, GLP1R_LSN1, GLP1R_LSN1_41Y, GLP1R_LSN1_V6G, GLP1R_LSN2, GLP1R_LSN2_41Y, GLP1R_LSN2_V6G, GIPR_ORFO, GIPR_ORFO_41Y, GIPR_ORFO_V6G, GIPR_LSN1, GIPR_LSN1_41Y, GIPR_LSN1_V6G, GIPR_LSN2, GIPR_LSN2_41Y, GIPR_LSN2_V6G, GLPAP, GIPAP
Predict affinity	yes	pIC50 predicted for every ligand-bound prediction
Ligand chemistry	2 of 3 flagged	LSN1, LSN2 -- see "Ligand preparation" below
Boltz predict runtime	20h 17m 13s	across 51 run invocations
Accelerator	gpu	gpu = Metal/CUDA backend used; cpu = no GPU available
Workers	2	parallel data-loading workers (Boltz's own default is 2)
MPS watermark	1.0	PYTORCH_MPS_HIGH_WATERMARK_RATIO cap -- lower avoids swap on Apple unified memory
Max parallel samples	1	Boltz's own --max_parallel_samples
Max MSA sequences	4096	cap on MSA sequences used for co-evolution features

Reference structures

The experimental structures this campaign was built on: where each pocket came from, and what the secondary-structure comparison measures against.

Pocket definitions

Pocket	From	Proteins	Contacts
41Y	7RBT	GIPR, GLP1R	74
V6G	7E14	GIPR, GLP1R	121

Secondary-structure references

Protein	Structure	State	Contents	Chain
GLP1R	5vew.cif	no G protein bound	2 chain(s), bound: 97Y	A
GIPR	8wa3.cif	active (G protein bound)	5 chain(s), bound: none	auto

State is read from the file, not from its title. A structure titled “apo” is often ligand-free and G-protein-coupled, which is the active state.

Ligand definitions

Ligand	Class	Given as	Experimental structure
ORFO	Control	SMILES	V6G
LSN1	Control	SMILES	41Y
LSN2	Control	SMILES	none

A control has been verified experimentally, by structure or by assay, so its prediction can be checked; an experimental compound is under investigation, with nothing to check against. Experimental compounds are ringed in red in the charts.

Summary table

Identity							Affinity		▸ Confidence (6)	▸ Interactions (7)	Structure
Run	Protein	Partner	Ligand	Pocket	Class	Summary	Binder p	pIC50	Score	pTM	ipTM	Lig ipTM	PPI ipTM	pLDDT	Total	Phobic	H-bond	π-stack	Halogen	π-cation	Salt	CIF
11	GIPR	GNAS, GNB1, GNG2	ORFO	41Y	Control		0.27	11.38	0.84	0.88	0.90	0.97	0.89	0.82	11.00	11	0	0	0	0	0	CIF
2	GLP1R	GNAS, GNB1, GNG2	ORFO	41Y	Control		0.58	11.18	0.83	0.88	0.88	0.97	0.88	0.82	7.00	7	0	0	0	0	0	CIF
12	GIPR	GNAS, GNB1, GNG2	ORFO	V6G	Control		0.45	10.47	0.83	0.87	0.87	0.91	0.87	0.82	13.00	10	2	0	0	1	0	CIF
3	GLP1R	GNAS, GNB1, GNG2	ORFO	V6G	Control		0.55	10.24	0.83	0.87	0.87	0.96	0.86	0.82	14.00	10	3	1	0	0	0	CIF
10	GIPR	GNAS, GNB1, GNG2	ORFO	Unc	Control		0.32	9.54	0.79	0.79	0.76	0.82	0.76	0.79	13.00	12	0	1	0	0	0	CIF
5	GLP1R	GNAS, GNB1, GNG2	LSN1	41Y	Control		0.89	9.48	0.84	0.92	0.92	0.99	0.91	0.82	13.00	11	1	1	0	0	0	CIF
1	GLP1R	GNAS, GNB1, GNG2	ORFO	Unc	Control		0.49	9.19	0.76	0.80	0.75	0.80	0.75	0.77	14.00	12	2	0	0	0	0	CIF
14	GIPR	GNAS, GNB1, GNG2	LSN1	41Y	Control		0.74	8.85	0.85	0.89	0.90	0.98	0.90	0.84	11.00	9	1	1	0	0	0	CIF
8	GLP1R	GNAS, GNB1, GNG2	LSN2	41Y	Control		0.65	8.72	0.85	0.91	0.91	0.99	0.91	0.83	9.00	7	1	1	0	0	0	CIF
18	GIPR	GNAS, GNB1, GNG2	LSN2	V6G	Control		0.53	8.57	0.82	0.86	0.87	0.88	0.87	0.81	12.00	6	5	0	0	0	1	CIF
9	GLP1R	GNAS, GNB1, GNG2	LSN2	V6G	Control		0.60	8.40	0.83	0.89	0.88	0.95	0.88	0.82	12.00	9	1	1	0	1	0	CIF
17	GIPR	GNAS, GNB1, GNG2	LSN2	41Y	Control		0.70	8.40	0.84	0.87	0.88	0.99	0.88	0.83	11.00	9	1	1	0	0	0	CIF
15	GIPR	GNAS, GNB1, GNG2	LSN1	V6G	Control		0.54	8.35	0.83	0.87	0.88	0.92	0.88	0.82	11.00	8	2	0	0	0	1	CIF
6	GLP1R	GNAS, GNB1, GNG2	LSN1	V6G	Control		0.60	8.26	0.84	0.89	0.88	0.95	0.88	0.83	18.00	13	3	2	0	0	0	CIF
13	GIPR	GNAS, GNB1, GNG2	LSN1	Unc	Control		0.28	8.12	0.77	0.75	0.70	0.61	0.71	0.78	17.00	15	2	0	0	0	0	CIF
4	GLP1R	GNAS, GNB1, GNG2	LSN1	Unc	Control		0.47	7.84	0.77	0.77	0.73	0.68	0.73	0.78	16.00	12	3	0	1	0	0	CIF
16	GIPR	GNAS, GNB1, GNG2	LSN2	Unc	Control		0.49	7.70	0.73	0.73	0.69	0.44	0.70	0.75	22.00	18	4	0	0	0	0	CIF
7	GLP1R	GNAS, GNB1, GNG2	LSN2	Unc	Control		0.56	7.70	0.75	0.76	0.71	0.68	0.72	0.76	7.00	6	0	0	0	1	0	CIF
19	GLPAP	GNAS, GNB1, GNG2	Apo	N/A	N/A	N/A	N/A	N/A	0.82	0.86	N/A	N/A	N/A	0.81	N/A	N/A	N/A	N/A	N/A	N/A	N/A	CIF
20	GIPAP	GNAS, GNB1, GNG2	Apo	N/A	N/A	N/A	N/A	N/A	0.83	0.86	N/A	N/A	N/A	0.82	N/A	N/A	N/A	N/A	N/A	N/A	N/A	CIF

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🎯 affinity · 🛡️ confidence: Likely binder (p ≥ 0.7) Uncertain (0.3-0.7) Likely non-binder (p < 0.3) High confidence (≥ 0.7) Moderate confidence (0.5-0.7) Low confidence (< 0.5)

Pockets

2 named pocket(s) (41Y, V6G) plus an unconstrained baseline; contacts are enforced within 4 A.

Pocket	Protein	Ligands	Runs	Targets	Contacts
41Y	GIPR	ORFO, LSN1, LSN2	11, 14, 17	3	37 residue(s)
41Y	GLP1R	ORFO, LSN1, LSN2	2, 5, 8	3	37 residue(s)
V6G	GIPR	ORFO, LSN1, LSN2	12, 15, 18	3	59 residue(s)
V6G	GLP1R	ORFO, LSN1, LSN2	3, 6, 9	3	62 residue(s)
Unconstrained	GIPR	ORFO, LSN1, LSN2	10, 13, 16	3	none -- ligand placed freely
Unconstrained	GLP1R	ORFO, LSN1, LSN2	1, 4, 7	3	none -- ligand placed freely

Ligand pose vs experiment

6 target(s) compared against experimental structures in reference/. Atoms are paired by molecular graph, so the symmetry of the ligand is respected rather than being resolved by whichever atom happened to be nearest. Not compared: 7E14 is not a structure of GIPR; 7RBT is not a structure of GLP1R.

Target	Protein	Ligand	Pocket	Reference	Site (A)	Pose (A)	Conformer (A)
GIPR_LSN1_41Y	GIPR	LSN1	41Y	7RBT (41Y)	0.66	0.91	0.51
GLP1R_ORFO_V6G	GLP1R	ORFO	V6G	7E14 (V6G)	1.85	2.79	1.63
GIPR_LSN1	GIPR	LSN1	unconstrained	7RBT (41Y)	6.00	6.17	0.81
GLP1R_ORFO	GLP1R	ORFO	unconstrained	7E14 (V6G)	11.64	13.57	2.92
GIPR_LSN1_V6G	GIPR	LSN1	V6G	7RBT (41Y)	22.88	24.92	1.78
GLP1R_ORFO_41Y	GLP1R	ORFO	41Y	7E14 (V6G)	28.23	29.40	3.67

🎯 site · pose: Same site (< 2 A) Nearby (2-5 A) Elsewhere (≥ 5 A) Pose reproduced (< 2 A) Approximate (2-5 A) Different pose (≥ 5 A)

Predicted against experimental

6 pair(s) across 3 pocket(s). Each frame holds exactly two ligands, superposed through their receptors: the prediction in red, the experimental one in grey.

Pocket 41Y

GIPR_LSN1_41Y0.91 Å

Grey: 7RBT 41Y. Red: predicted.

GLP1R_ORFO_41Y29.40 Å

Grey: 7E14 V6G. Red: predicted.

Pocket V6G

GLP1R_ORFO_V6G2.79 Å

Grey: 7E14 V6G. Red: predicted.

GIPR_LSN1_V6G24.92 Å

Grey: 7RBT 41Y. Red: predicted.

Unconstrained

GIPR_LSN16.17 Å

Grey: 7RBT 41Y. Red: predicted.

GLP1R_ORFO13.57 Å

Grey: 7E14 V6G. Red: predicted.

Ligand preparation

2 of 3 ligand(s) flagged for chemistry review -- these are advisory, not errors; verify the input SMILES reflects what you intended before trusting the results below.

Ligand	Chemistry notes
LSN1	ionizable group(s) present (primary/secondary amine, phenol) -- verify the SMILES reflects your intended protonation state
LSN2	ionizable group(s) present (phenol) -- verify the SMILES reflects your intended protonation state

Ligand structures

shared scaffold -- 2/3 ligandsSundefined stereocentreAcarboxylic acidNprimary/secondary aminePhphenolSO3sulfonic acidsaltsalt/disconnected fragment

ORFO

MW 883 · cLogP 7.4 · TPSA 156

LSN1NPh

MW 505 · cLogP 8.1 · TPSA 45

LSN2Ph

MW 462 · cLogP 5.8 · TPSA 62

Download PDF · Download SMILES

Scaffolds: Bemis-Murcko, exact match first, then Tanimoto-clustered (Morgan r=2, 2048-bit, threshold 0.60) whole-group MCS as a verified fallback. Minimum highlighted substructure size: 8 heavy atoms. Stereocentre/ionizable-group highlighting from this campaign's own ligand-preparation check (see above).

1_GLP1R_GNAS+GNB1+GNG2_ORFO_Unc: binding site

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Interaction	Residue	Number	Chain	Distance
hydrogen bonds	ARG	43	A	2.60
hydrogen bonds	VAL	405	A	3.84
hydrophobic	LEU	12	A	3.66
hydrophobic	LYS	351	A	2.85
hydrophobic	LEU	354	A	3.38
hydrophobic	THR	355	A	3.35
hydrophobic	GLU	392	B	3.52
hydrophobic	PHE	393	A	3.61
hydrophobic	LEU	396	A	3.32
hydrophobic	LEU	401	A	3.67
hydrophobic	VAL	405	A	3.80
hydrophobic	PRO	439	A	3.79
hydrophobic	PRO	439	A	3.65
hydrophobic	LEU	443	A	3.73

Interaction	Residue	Number	Chain	Distance
hydrophobic	PHE	324	A	3.93
hydrophobic	LEU	354	A	3.33
hydrophobic	ILE	357	A	3.66
hydrophobic	ILE	357	A	2.98
hydrophobic	HIS	363	A	3.43
hydrophobic	PHE	390	A	3.81
hydrophobic	LEU	401	A	3.07

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	LEU	32	A	3.57
hydrogen bonds	TRP	33	A	3.19
hydrogen bonds	LYS	197	A	3.86
hydrophobic	LEU	32	A	3.47
hydrophobic	LEU	32	A	3.85
hydrophobic	LEU	141	A	3.68
hydrophobic	TYR	145	A	3.44
hydrophobic	TYR	145	A	3.38
hydrophobic	TYR	145	A	3.71
hydrophobic	LEU	201	A	3.46
hydrophobic	TYR	220	A	3.31
hydrophobic	PHE	381	A	3.27
hydrophobic	PHE	381	A	2.81
pi stacks	PHE	385	A	4.13

Interaction	Residue	Number	Chain	Distance
halogen bonds	VAL	405	A	1.75
hydrogen bonds	VAL	405	A	3.56
hydrogen bonds	ASN	406	A	2.99
hydrogen bonds	ASN	407	A	3.88
hydrophobic	TRP	33	A	3.88
hydrophobic	GLN	37	A	3.65
hydrophobic	ARG	40	A	3.20
hydrophobic	ARG	40	A	3.99
hydrophobic	LYS	351	A	3.90
hydrophobic	PRO	358	A	3.80
hydrophobic	TYR	391	B	3.02
hydrophobic	LEU	401	A	3.82
hydrophobic	LEU	401	A	3.65
hydrophobic	TYR	402	A	2.91
hydrophobic	VAL	405	A	3.64
hydrophobic	ALA	447	A	3.46

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	PHE	390	A	2.72
hydrophobic	PHE	321	A	3.89
hydrophobic	PHE	324	A	3.68
hydrophobic	LEU	354	A	3.39
hydrophobic	ILE	357	A	3.83
hydrophobic	ILE	357	A	3.92
hydrophobic	PRO	358	A	3.90
hydrophobic	HIS	363	A	3.84
hydrophobic	ILE	366	A	3.64
hydrophobic	PHE	390	A	3.75
hydrophobic	PHE	390	A	3.83
hydrophobic	PHE	393	A	3.86
pi stacks	HIS	363	A	5.04

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	THR	298	A	3.28
hydrogen bonds	THR	298	A	3.28
hydrogen bonds	GLN	221	A	3.15
hydrophobic	THR	29	A	3.47
hydrophobic	PHE	385	A	3.33
hydrophobic	PHE	381	A	3.43
hydrophobic	TYR	220	A	3.18
hydrophobic	TYR	205	A	3.91
hydrophobic	LYS	202	A	3.82
hydrophobic	LEU	201	A	3.43
hydrophobic	LEU	201	A	3.46
hydrophobic	LYS	197	A	3.39
hydrophobic	TYR	145	A	3.44
hydrophobic	TYR	145	A	3.42
hydrophobic	LEU	141	A	3.39
hydrophobic	LEU	32	A	2.74
pi stacks	TYR	145	A	3.99
pi stacks	PHE	381	A	3.89

Interaction	Residue	Number	Chain	Distance
hydrophobic	TRP	39	A	4.00
hydrophobic	PHE	187	A	3.38
hydrophobic	LEU	244	A	3.05
hydrophobic	THR	391	A	3.67
hydrophobic	GLN	394	A	3.13
hydrophobic	TRP	417	A	3.77
pi cation	HIS	363	A	3.77

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	PHE	390	A	2.62
hydrophobic	PHE	324	A	3.24
hydrophobic	LEU	354	A	3.43
hydrophobic	ILE	357	A	3.67
hydrophobic	ILE	366	A	3.73
hydrophobic	PHE	390	A	3.86
hydrophobic	PHE	390	A	3.78
hydrophobic	PHE	393	A	3.71
pi stacks	HIS	363	A	5.16

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	LEU	144	A	3.87
hydrophobic	THR	29	A	3.37
hydrophobic	LEU	141	A	3.57
hydrophobic	TYR	145	A	3.24
hydrophobic	LYS	197	A	3.97
hydrophobic	ALA	200	A	3.34
hydrophobic	LEU	201	A	3.19
hydrophobic	TYR	220	A	3.44
hydrophobic	PHE	385	A	3.74
hydrophobic	PHE	385	A	3.98
pi cation	LYS	197	A	5.71
pi stacks	PHE	385	A	4.09

Interaction	Residue	Number	Chain	Distance
hydrophobic	LEU	337	A	3.72
hydrophobic	LEU	344	A	3.00
hydrophobic	LEU	344	A	3.67
hydrophobic	VAL	347	A	3.76
hydrophobic	PHE	376	A	3.75
hydrophobic	PHE	379	A	3.93
hydrophobic	LEU	380	A	3.06
hydrophobic	LEU	391	A	3.37
hydrophobic	ILE	395	A	3.31
hydrophobic	THR	442	A	3.38
hydrophobic	LEU	446	A	3.52
hydrophobic	LEU	451	A	3.09
pi stacks	HIS	353	A	4.62

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	PHE	383	A	4.02
hydrogen bonds	LEU	380	A	2.58
hydrophobic	ALA	458	A	3.86
hydrophobic	PRO	454	A	3.68
hydrophobic	LEU	451	A	3.59
hydrophobic	LEU	387	A	3.90
hydrophobic	LEU	387	A	2.84
hydrophobic	PHE	383	A	3.12
hydrophobic	LEU	9	A	3.24
hydrophobic	PHE	379	A	3.65
hydrophobic	VAL	356	A	3.25
hydrophobic	PRO	348	A	3.62
hydrophobic	VAL	347	A	3.57
hydrophobic	LEU	344	A	3.56
hydrophobic	PHE	314	A	3.31
hydrophobic	LEU	380	A	3.72
hydrophobic	LEU	380	A	3.43

Family	Status	Detail
GLP1R_GNAS+GNB1+GNG2	OK	90 motif row(s) across 9 target(s), annotator=gpcr
GIPR_GNAS+GNB1+GNG2	OK	90 motif row(s) across 9 target(s), annotator=gpcr
GLPAP_GNAS+GNB1+GNG2	No apo structure configured	No 'Apo structure:' configured for this family
GIPAP_GNAS+GNB1+GNG2	No apo structure configured	No 'Apo structure:' configured for this family

Identity						Shift			Helix geometry				Boundary		Backbone
Family	Target	Ligand	Motif	Kind	Source	N res	RMSD (A)	Centroid delta (A)	Axis rot (deg)	Kink apo (deg)	Kink holo (deg)	Kink delta (deg)	Start delta	End delta	Flagged phi/psi
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	17	1.20	0.64	6.17	13.34	11.05	-2.29	1.00	2.00	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	17	1.12	0.87	4.03	13.34	9.39	-3.96	1.00	2.00	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	17	1.18	0.91	4.21	13.34	9.13	-4.21	1.00	7.00	0
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	20	2.04	1.69	5.93	5.05	11.74	6.69	142.00	150.00	3
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	20	2.06	1.67	6.18	5.05	12.27	7.22	142.00	149.00	3
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	H8	helix	gpcr	20	1.73	1.50	2.95	5.05	8.78	3.74	142.00	149.00	3
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	32	1.08	0.76	1.24	3.49	10.54	7.05	N/A	N/A	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	32	1.75	1.21	4.77	3.49	7.96	4.47	N/A	N/A	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	32	1.34	1.01	2.98	3.49	6.12	2.63	N/A	N/A	1
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	35	3.15	1.99	7.85	8.70	16.12	7.42	N/A	N/A	2
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	35	3.69	2.13	9.85	8.70	15.54	6.84	N/A	N/A	2
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM1	helix	gpcr	35	4.60	2.60	11.82	8.70	23.20	14.50	N/A	N/A	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	2.24	0.68	3.58	17.56	6.33	-11.23	N/A	N/A	4
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	1.30	0.56	3.02	17.56	15.36	-2.20	N/A	N/A	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	1.80	0.80	5.31	17.56	12.38	-5.19	N/A	N/A	2
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	0.93	0.59	2.07	4.18	12.85	8.68	N/A	N/A	1
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	0.88	0.64	1.23	4.18	10.38	6.20	N/A	N/A	0
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM2	helix	gpcr	28	0.99	0.79	0.37	4.18	12.14	7.96	N/A	N/A	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	32	1.19	0.70	2.42	15.22	17.44	2.22	N/A	N/A	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	32	1.30	0.91	1.65	15.22	17.50	2.28	N/A	N/A	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	32	1.30	0.91	1.85	15.22	16.20	0.98	N/A	N/A	3
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	37	1.08	0.49	2.57	16.75	17.04	0.29	N/A	N/A	1
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	37	0.93	0.72	0.58	16.75	14.80	-1.95	N/A	N/A	0
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM3	helix	gpcr	37	1.11	0.85	1.80	16.75	14.58	-2.17	N/A	N/A	0
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	29	0.76	0.23	2.21	10.55	7.01	-3.54	-11.00	-2.00	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	29	0.91	0.35	2.33	10.55	8.39	-2.16	-12.00	-2.00	2
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	29	1.14	0.55	3.08	10.55	8.57	-1.98	-12.00	-2.00	4
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	27	1.14	0.95	0.76	4.63	7.06	2.43	125.00	119.00	3
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	27	1.38	1.20	1.25	4.63	3.79	-0.83	124.00	120.00	3
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM4	helix	gpcr	27	1.71	1.51	2.45	4.63	3.33	-1.29	124.00	120.00	3
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	2.17	0.72	2.24	7.73	20.05	12.32	1.00	0.00	7
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	2.58	1.33	3.90	7.73	18.63	10.90	1.00	0.00	7
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	2.61	1.26	4.63	7.73	18.98	11.26	1.00	0.00	7
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	1.24	1.02	1.20	18.00	16.71	-1.30	126.00	134.00	1
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	1.20	0.85	2.15	18.00	14.72	-3.29	126.00	134.00	0
GIPR_GNAS+GNB1+GNG2	GIPR_GNAS+GNB1+GNG2_LSN1	LSN1	TM5	helix	gpcr	35	1.32	0.88	2.78	18.00	14.58	-3.42	126.00	133.00	1
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM6	helix	gpcr	28	9.36	5.68	24.93	19.85	74.11	54.26	-2.00	-7.00	6
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM6	helix	gpcr	28	8.86	5.10	24.15	19.85	67.42	47.57	-2.00	-7.00	6
GLP1R_GNAS+GNB1+GNG2	GLP1R_GNAS+GNB1+GNG2_LSN1	LSN1	TM6	helix	gpcr	28	9.17	5.51	22.90	19.85	75.44	55.59	-2.00	-7.00	8

Targets	20 predicted, 18 with a ligand
Receptors	GIPAP, GIPR, GLP1R, GLPAP
Ligands	LSN1, LSN2, ORFO
Verdicts	10 proceed, 6 caution, 4 discard
Confidence	14 well determined, 6 moderately determined
Flagged	10 of 20
Pose validated	1 of 6 reproduced the experimental pose

Target	Verdict	Summary	Caveat	Written by
`GLP1R_ORFO`	discard	The structure is moderately determined, meaning it is likely correct but not certain. This is a good indication for scientists who need a reliable structure for further studies. The ORFO ligand is a control ligand, and it made 14 contacts with the receptor, 12 of which were hydrophobic. The predicted potency of the ORFO ligand is 9.19, which is lower than the experimental pic50 of 0.48. The ORFO ligand is ranked 7th out of 18 ligands in terms of predicted potency.	The predicted pose does not reproduce the experimental structure, meaning that the predicted position of the ORFO ligand is not consistent with the experimental structure.	model
`GLP1R_ORFO_41Y`	discard	The structure is well determined: confidence 0.83, ipTM 0.884, ligand ipTM 0.973. ORFO (control) at 41Y: predicted pIC50 11.18, binder probability 0.579, ranked 2 of 18 by predicted potency. Interactions: 7 in total: 7 hydrophobic contacts. Against 7E14 the prediction does not reproduce the experimental pose (pose 29.4 Å).	the predicted pose disagrees with the experimental structure.	template
`GLP1R_ORFO_V6G`	proceed	The structure is well determined: confidence 0.831, ipTM 0.869, ligand ipTM 0.962. ORFO (control) at V6G: predicted pIC50 10.24, binder probability 0.555, ranked 4 of 18 by predicted potency. Interactions: 14 in total: 10 hydrophobic contacts, 3 hydrogen bonds, 1 pi-stack. Against 7E14 the prediction close to the experimental pose (pose 2.79 Å).	Nothing was flagged for this target.	template
`GLP1R_LSN1`	caution	This structure is moderately determined. Such a determination level suggests that the structure is reliable, but it is not definitive. LSN1 was poorly placed relative to the receptor	Overall confidence is below the well-determined threshold	model
`GLP1R_LSN1_41Y`	proceed	This structure is well determined and reliable for further investigation. LSN1 is a control ligand with 13 contacts in total, 11 hydrophobic contacts, 1 hydrogen bond, and 1 pi-stack. Its predicted potency is 9.48 and it ranks 6 of 18 by predicted potency.	The largest caveat is that there are no flags indicating any issues with the structure.	model
`GLP1R_LSN1_V6G`	proceed	Well determined. A good score for confidence. LSN1 is a control ligand with 18 contacts in total, 13 hydrophobic contacts, 3 hydrogen bonds, and 2 pi-stacks. Its predicted potency is 8.26, which is 14th of 18 ligands by predicted potency.	No flags were present, so nothing is amiss.	model
`GLP1R_LSN2`	caution	The structure is moderately determined, meaning that while it's reasonably certain, there's still some uncertainty about its accuracy. LSN2, a control ligand, made 7 contacts with the receptor, 6 of which were hydrophobic and 1 was a pi-cation interaction. Its predicted potency is 7.7, placing it 18th out of 18 predicted potencies for this receptor. The predicted potency was not reproduced by the experimental structure.	Overall confidence is below the well-determined threshold and the ligand is poorly placed relative to the receptor.	model
`GLP1R_LSN2_41Y`	proceed	This structure is well determined, with high confidence scores across several metrics. LSN2 is a control ligand with 9 contacts, including 7 hydrophobic and 1 hydrogen bond, and a predicted potency of 8.72 nM, ranking 9th out of 18 ligands by predicted potency.	There are no flags indicating any issues with the structure.	model
`GLP1R_LSN2_V6G`	proceed	The structure of GLP1R, when compared against the apo or inactive reference, is well determined. LSN2 is a control ligand, and the structure is predicted to be 11th in potency among 18 ligands tested, with 9 hydrophobic contacts, 1 hydrogen bond, 1 pi-stack and 1 pi-cation interaction in the pocket V6G.	No flags were found. However, the structure was not predicted to reproduce the experimental structure, which is a caveat.	model
`GIPR_ORFO`	caution	The structure is moderately determined, meaning it's likely to be correct, but it's not as certain as a well-determined structure. This should be taken into account when deciding whether to trust the structure. ORFO is a control ligand that interacted with the receptor GIPR. It made 12 hydrophobic contacts and one pi-stack, and its predicted potency is 9.54 times the experimental value. This suggests that ORFO is a weak ligand, and it might not be a good starting point for further studies on the receptor's binding preferences.	The overall confidence is below the well-determined threshold, which means that the structure is not as certain as it should be. This suggests that there might be some uncertainty in the structure, and it's important to be cautious when interpreting the results.	model
`GIPR_ORFO_41Y`	proceed	This structure is well determined, and that means it is reliable for someone deciding whether to trust it. ORFO is a control ligand with 11 hydrophobic contacts and a predicted potency of 11.38 nM, ranking 1 of 18 by predicted potency.	There are no flags, and nothing is amiss.	model
`GIPR_ORFO_V6G`	proceed	This structure is well determined and is likely to be reliable for further study. ORFO is a control ligand with 10 hydrophobic contacts, 2 hydrogen bonds, and 1 pi-cation interaction. The predicted potency is 10.47, placing it 3rd out of 18 ligands by predicted potency.	There are no flags indicating any issues with the structure.	model
`GIPR_LSN1`	discard	The predicted structure of this target is moderately determined, meaning that there is some uncertainty, but it is not so great that it is impossible to trust. LSN1 is poorly placed relative to the receptor, and the predicted potency varies widely across the ensemble	Overall confidence is below the well-determined threshold	model
`GIPR_LSN1_41Y`	proceed	The structure is well determined: confidence 0.854, ipTM 0.905, ligand ipTM 0.984. LSN1 (control) at 41Y: predicted pIC50 8.85, binder probability 0.742, ranked 8 of 18 by predicted potency. Interactions: 11 in total: 9 hydrophobic contacts, 1 hydrogen bond, 1 pi-stack. Against 7RBT the prediction reproduces the experimental pose (pose 0.91 Å).	Nothing was flagged for this target.	template
`GIPR_LSN1_V6G`	discard	The predicted structure is well determined, with scores indicating that the predicted pose and structure are very close to the experimental structure. LSN1 is a control ligand with 11 total contacts, mostly hydrophobic, and a predicted potency of 8.35. It ranks 13th out of 18 ligands by predicted potency.	The predicted pose does not reproduce the experimental structure.	model
`GIPR_LSN2`	caution	The structure is moderately determined, indicating that while it is reasonably accurate, it may still contain some uncertainties that could affect its reliability. LSN2 is poorly positioned relative to the receptor and has a predicted potency of 7.7, placing it 17th out of 18 ligands in predicted potency.	Overall confidence is below the well-determined threshold, and the ligand is poorly placed relative to the receptor.	model
`GIPR_LSN2_41Y`	proceed	Well determined. This is an indication that the structure is very likely correct. For someone deciding whether to trust it, this is a good thing. LSN2 is a control ligand. It has a predicted potency of 8.4. It has 11 total contacts, 9 hydrophobic, 1 hydrogen bond, and 1 pi-stack. It is not specified what the role of LSN2 is in this structure.	There are no flags in this structure.	model
`GIPR_LSN2_V6G`	proceed	The structure is well determined, and the confidence score is close to 1.0, so it is likely to be accurate. LSN2 is a control ligand that was used to establish a baseline for potency prediction. It has 12 contacts in total, with 6 hydrophobic and 5 hydrogen bonds, and it was predicted to have a potency of 8.57 µM, which is higher than the experimental pic50 value of 0.55 µM. However, the predicted potency is still 10th of 18 by predicted potency, suggesting that it is not the most potent ligand in this set.	There are no flags, so the structure is not flagged as a failed prediction.	model
`GLPAP`	caution	The structure is well determined, and the high confidence scores indicate that this prediction is trustworthy for scientists deciding whether to trust it.	The ligand is poorly placed relative to the receptor, and interaction analysis did not complete for this target.	model
`GIPAP`	caution	The structure is well determined, meaning it is likely to be correct and reliable for further research.	The ligand is poorly placed relative to the receptor and interaction analysis did not complete for this target.	model

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	GLN	224	A	3.01
hydrogen bonds	ASN	290	A	4.03
hydrophobic	LEU	134	A	3.79
hydrophobic	LEU	134	A	3.64
hydrophobic	GLU	135	A	3.31
hydrophobic	GLN	138	A	3.62
hydrophobic	LEU	194	A	3.84
hydrophobic	PRO	197	A	3.86
hydrophobic	TRP	296	A	3.87
hydrophobic	LEU	374	A	3.91
salt bridges	ASP	191	A	5.40

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	THR	450	A	2.89
hydrogen bonds	GLN	384	A	3.25
hydrogen bonds	PHE	383	A	4.06
hydrogen bonds	GLN	384	A	3.69
hydrophobic	THR	450	A	3.50
hydrophobic	LEU	393	B	3.66
hydrophobic	TYR	392	A	2.63
hydrophobic	TYR	392	A	2.74
hydrophobic	TYR	391	B	3.36
hydrophobic	LEU	391	A	3.14
hydrophobic	VAL	388	A	3.77
hydrophobic	ALA	32	A	3.22
hydrophobic	LEU	380	A	3.49
hydrophobic	LEU	349	A	2.56
hydrophobic	LEU	349	A	1.36
hydrophobic	PRO	348	A	1.40
hydrophobic	PRO	348	A	2.03
hydrophobic	LEU	346	A	3.13
hydrophobic	THR	345	A	3.21
hydrophobic	LEU	241	A	3.67
hydrophobic	PHE	383	A	2.68
hydrophobic	LEU	387	A	2.20

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	LEU	380	A	2.39
hydrophobic	PHE	311	A	3.63
hydrophobic	PHE	314	A	3.70
hydrophobic	LEU	344	A	3.47
hydrophobic	VAL	347	A	3.98
hydrophobic	VAL	347	A	3.74
hydrophobic	HIS	353	A	3.76
hydrophobic	VAL	356	A	3.96
hydrophobic	LEU	380	A	3.37
hydrophobic	LEU	387	A	3.24
pi stacks	HIS	353	A	4.89

Interaction	Residue	Number	Chain	Distance
hydrogen bonds	TYR	141	A	4.01
hydrogen bonds	ARG	190	A	2.64
hydrogen bonds	ASP	191	A	4.05
hydrogen bonds	ASN	290	A	3.65
hydrogen bonds	ARG	370	A	2.77
hydrophobic	ILE	187	A	3.58
hydrophobic	ARG	289	A	3.69
hydrophobic	LEU	374	A	4.00
hydrophobic	GLU	377	A	3.93
hydrophobic	ILE	378	A	3.52
hydrophobic	ILE	378	A	3.74
salt bridges	ASP	191	A	5.18

Campaign summary

Reference structures

Pocket definitions

Secondary-structure references

Ligand definitions

Summary table

Pockets

Ligand pose vs experiment

Predicted against experimental

Pocket 41Y

Pocket V6G

Unconstrained

Ligand preparation

Ligand structures

pIC50 vs confidence score

Interaction counts by type

pIC50 vs binder probability

Ranked predicted pIC50

Ranked confidence

GIPR_GNAS+GNB1+GNG2: residue interaction fingerprint

GLP1R_GNAS+GNB1+GNG2: residue interaction fingerprint

1_GLP1R_GNAS+GNB1+GNG2_ORFO_Unc: binding site

2_GLP1R_GNAS+GNB1+GNG2_ORFO_41Y: binding site

3_GLP1R_GNAS+GNB1+GNG2_ORFO_V6G: binding site

4_GLP1R_GNAS+GNB1+GNG2_LSN1_Unc: binding site

5_GLP1R_GNAS+GNB1+GNG2_LSN1_41Y: binding site

6_GLP1R_GNAS+GNB1+GNG2_LSN1_V6G: binding site

7_GLP1R_GNAS+GNB1+GNG2_LSN2_Unc: binding site

8_GLP1R_GNAS+GNB1+GNG2_LSN2_41Y: binding site

9_GLP1R_GNAS+GNB1+GNG2_LSN2_V6G: binding site

10_GIPR_GNAS+GNB1+GNG2_ORFO_Unc: binding site

11_GIPR_GNAS+GNB1+GNG2_ORFO_41Y: binding site

12_GIPR_GNAS+GNB1+GNG2_ORFO_V6G: binding site

13_GIPR_GNAS+GNB1+GNG2_LSN1_Unc: binding site

14_GIPR_GNAS+GNB1+GNG2_LSN1_41Y: binding site

15_GIPR_GNAS+GNB1+GNG2_LSN1_V6G: binding site

16_GIPR_GNAS+GNB1+GNG2_LSN2_Unc: binding site

17_GIPR_GNAS+GNB1+GNG2_LSN2_41Y: binding site

18_GIPR_GNAS+GNB1+GNG2_LSN2_V6G: binding site

Family coverage and SSE shifts

Per-motif Ca RMSD

Selectivity and motif shifts

Family x ligand selectivity

Motif x target RMSD

Landlord narration

Key findings

Highest predicted potency

Caveats

Per target