BoltzMaker Report | Marc C. Deller

Campaign summary

Field	Value	Details
Input file	boltz_input.md	boltz_input.md
Proteins	2	HTR2A (471 aa); HTRAP (471 aa)
Co-folded partners	3	GNAI1 (protein, 354 aa); GNB1 (protein, 340 aa); GNG2 (protein, 71 aa)
Ligands	1	8NU (SMILES)
Pockets	0	none -- every ligand folded without a site constraint
Apo structure references	1	HTRAP
Predictions	2	HTR2A_8NU, HTRAP
Predict affinity	yes	pIC50 predicted for every target
Ligand chemistry	clean	no stereo/protonation/fragment concerns detected
Boltz predict runtime	1h 43m 52s	across 2 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

Summary table

Identity				Affinity		Confidence						Interactions					Structure
Protein	Partner	Ligand	Summary	Binder p	pIC50	Score	pTM	ipTM	Lig ipTM	PPI ipTM	pLDDT	Phobic	π-stack	H-bond	Salt	Halogen	CIF
HTR2A	GNAI1, GNB1, GNG2	8NU		0.99	12.73 ± 0.20	0.81	0.88	0.85	0.95	0.85	0.81	5	2	1	1	1	CIF
HTRAP	GNAI1, GNB1, GNG2	N/A	N/A	N/A	N/A	0.80	0.88	N/A	N/A	N/A	0.78	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

No named pockets in this campaign -- every ligand was placed without a site constraint.

Pocket	Protein	Ligands	Targets	Contacts
Unconstrained	HTR2A	8NU	1	none -- ligand placed freely

Ligand preparation

No stereocentre, protonation-state, or disconnected-fragment concerns detected.

Ligand structures

Sundefined stereocentreAcarboxylic acidNprimary/secondary aminePhphenolSO3sulfonic acidsaltsalt/disconnected fragment

8NU

MW 410 · cLogP 3.6 · TPSA 64

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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).

Ranked predicted pIC50

Ranked confidence

Family x ligand selectivity

pIC50 vs confidence score

Interaction counts by type

pIC50 vs binder probability

HTR2A_GNAI1+GNB1+GNG2: residue interaction fingerprint

HTR2A_GNAI1+GNB1+GNG2_8NU: binding site

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Interaction	Residue	Number	Chain	Distance
halogen bonds	PHE	234	A	3.18
hydrogen bonds	SER	159	A	3.91
hydrophobic	VAL	156	A	3.96
hydrophobic	VAL	156	A	3.99
hydrophobic	LEU	228	A	2.76
hydrophobic	LEU	229	A	3.86
hydrophobic	PHE	339	A	3.61
pi stacks	PHE	340	A	5.09
pi stacks	PHE	340	A	5.25
salt bridges	ASP	155	A	2.87

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Secondary structure shifts (apo vs holo)

Family	Status	Detail
HTR2A_GNAI1+GNB1+GNG2	OK	13 motif row(s) across 1 target(s), annotator=gpcr
HTRAP_GNAI1+GNB1+GNG2	No apo structure configured	No 'Apo structure:' configured for this family

1 target(s), 13 motif(s) compared
Mean Ca RMSD: 1.03 A (median 0.92 A) — largest shift: 2.50 A at HTR2A_GNAI1+GNB1+GNG2_8NU / ICL2
Mean centroid shift: 0.77 A
Flagged phi/psi outlier residues: 19
Kinase state changes detected: 0 DFG, 0 alphaC

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
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	H8	helix	gpcr	10	0.85	0.76	3.82	18.98	23.78	4.80	142.00	134.00	0
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM1	helix	gpcr	25	1.09	0.97	1.36	10.92	6.30	-4.62	N/A	N/A	2
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM2	helix	gpcr	31	0.84	0.56	1.49	19.22	21.79	2.57	N/A	N/A	1
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM3	helix	gpcr	36	0.61	0.17	0.60	7.36	11.03	3.67	66.00	77.00	0
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM4	helix	gpcr	30	0.86	0.44	0.82	24.62	27.32	2.70	82.00	80.00	0
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM5	helix	gpcr	31	1.00	0.87	1.10	9.07	9.40	0.33	85.00	86.00	3
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM6	helix	gpcr	35	0.74	0.68	0.06	29.00	29.19	0.18	124.00	140.00	1
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	TM7	helix	gpcr	30	0.69	0.21	1.35	29.08	26.93	-2.15	123.00	138.00	4
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	ECL1	loop	gpcr	4	1.00	0.94	N/A	N/A	N/A	N/A	N/A	N/A	2
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	ECL2	loop	gpcr	3	0.96	0.85	N/A	N/A	N/A	N/A	79.00	48.00	0
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	ICL1	loop	gpcr	4	0.92	0.89	N/A	N/A	N/A	N/A	N/A	N/A	2
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	ICL2	loop	gpcr	9	2.50	1.38	N/A	N/A	N/A	N/A	82.00	80.00	4
HTR2A_GNAI1+GNB1+GNG2	HTR2A_GNAI1+GNB1+GNG2_8NU	8NU	ICL3	loop	gpcr	1	1.33	1.33	N/A	N/A	N/A	N/A	N/A	N/A	0

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Per-motif Ca RMSD

Motif x target RMSD

Landlord narration

2 of 2 target summaries written on-device by the Apple Neural Engine; 0 rendered from the template. Every number here is checked against the figures the analysis computed; a summary stating one it was not given was replaced by the template.

The 5HT2A_GQ campaign tested the predicted structures of two receptors, HTR2A and HTRAP, using the ligand 8NU. One of the two targets, HTR2A_8NU, was deemed to be well-determined with a high binder probability, and was marked proceed. The other, HTRAP, was deemed to be moderately determined, and was marked caution.

Targets	2 predicted, 1 with a ligand
Receptors	HTR2A, HTRAP
Ligands	8NU
Verdicts	1 proceed, 1 caution
Confidence	1 well determined, 1 moderately determined
Flagged	1 of 2
Pose validated	no experimental structure to compare against

Key findings

Of 2 targets, 1 are marked proceed, 1 caution and 0 discard.
1 of 2 targets are well determined; 1 are not.
1 of 2 targets carry at least one flag.

Highest predicted potency

8NU on HTR2A_GNAI1+GNB1+GNG2_8NU, predicted pIC50 12.73

Caveats

The predicted structures of the two targets were not validated against experimental structures, limiting the confidence in the accuracy of the model.

Per target

Target	Verdict	Summary	Caveat	Written by
`HTR2A_8NU`	proceed	The predicted structure of the HTR2A_GNAI1+GNB1+GNG2_8NU target is well determined, with high confidence scores for complex PLDDT, IPTM, and PTM. This indicates that the structure is reliable and can be trusted for further analysis. The ligand 8NU has a binder probability of 0.994 and was ranked as the top predicted ligand by potency. However, the interaction analysis for 8NU was not run, so there is uncertainty about its actual binding properties.	The predicted structure was not validated against an experimental structure, which is a significant caveat as it limits the confidence in the accuracy of the model.	model
`HTRAP`	caution	The structure is moderately determined, meaning the data is consistent with a 3D model, but the confidence level is not extremely high. This suggests that while the model is likely correct, there is still some uncertainty.	Overall confidence is below the well-determined threshold, the ligand is poorly placed relative to the receptor, and interaction analysis did not complete for this target.	model