GOBSMACKED: gs_20260910

Score

84.1

GOBSMACK score, validity gate passed

carazolol through the run: 22 heavy atoms, flexing in place.

Ligand RMSD 1.41 A Close enough to be the same binding mode. Check the hinge H-bonds before trusting the details.

PLIP overlap 0.54 About half the crystal contacts are reproduced. Look at which type is missing: a lost hydrogen bond and a lost hydrophobic contact mean different things.

Pocket Ca RMSD 0.84 A The pocket backbone matches the crystal, so the ligand had somewhere correct to bind.

chi1 agreement 0.83 Pocket side chains are in the crystal rotamers.

Drift, last 200 ps 0.27 A The ligand stayed where docking put it for the whole run.

Pose validity

No ligand-protein heavy-atom contact under 2.2 A pass
Ligand bond lengths within 25 % of the ideal pass
Stereocentres unchanged from the input SMILES pass
Ligand centroid inside the docking box pass

Predicted affinity

	Docked pose	After MD, 5 frames	Change
pIC50	10.18	10.16 ± 0.01	-0.02
Boltz-2 value	-4.18	-4.16 ± 0.01	+0.02
Binder probability	1.00	1.00 ± 0.00	+0.00

Predicted pIC50 10.16 after MD, 0.02 log units weaker than the docked pose.

affinity_pred_value is log10(IC50) with IC50 in micromolar, lower is stronger; pIC50 = 6 - affinity_pred_value, higher is stronger.

Boltz-2's affinity head. The complex was held within 2 A of the structure this pipeline produced while Boltz-2 rebuilt it, so the head reads the docked and relaxed conformations rather than one of its own. It is not a free energy, it is not comparable across targets, and it is not evidence that the pose is correct: nothing here is weighed against a crystal, so none of it enters the score above.

Pocket backbone through MD: 0.32 → 0.84 Å from the crystal, so MD moved it 0.52 Å further away. Reported, not scored: in every run measured so far MD has moved the pocket away, so this says what happened rather than how well it went.

Complex

MD-final complex

Overlay

pocket Ca superposition

Motion

50 frames

The production run in full: 50 frames over 490 ps. Drag to turn, scroll to zoom, Play to run the trajectory.

Docked poses

7 poses

Every pose is in the right pocket and none is the right pose: the closest centre is 0.7 A from the crystal ligand's, while the best in-place RMSD is 3.6 A. Superposed freely, the ligand matches the crystal to 1.0 A, so it is folded about right and turned the wrong way round. Raise the exhaustiveness and tighten the box before suspecting the scoring function; a flexible-side-chain run is the next thing after that.

Pose ranking

#	Score	Vina	pEC50	Vinardo	RMSD	Centre	Shape	Contact
4	-15.12	—	—	-8.55	3.62	0.66	1.93	2.79
7	-14.86	—	—	-8.17	5.69	1.88	0.99	2.16
3	-15.68	—	—	-7.12	3.93	2.03	2.12	2.33
5	-16.28	—	—	-6.97	6.26	1.82	1.96	2.41
8	-14.20	—	—	-5.14	8.77	5.35	1.86	2.05
9	-16.44	—	—	2.76	3.98	0.72	1.48	2.50
6	-14.89	—	—	24.77	6.19	1.79	1.25	0.91

Score and Vina in kcal/mol; RMSD, Centre, Shape and Contact in A. RMSD is to the crystal ligand where it lies. Centre is the distance between the two centroids: it says whether the pose is in the right pocket at all. Shape is the RMSD after superposing the two ligands freely, which throws the placement away and asks only whether the molecule is folded the same. A low Centre and a low Shape beside a high RMSD is a ligand in the right site, turned the wrong way round. Contact is the closest heavy-atom approach to the receptor; under 2.2 A is a clash. Pose 1 went to MD; a highlighted row below it is the pose nearest the crystal.

Vinardo re-scored these same ten coordinates and decides which pose goes forward. It sampled nothing and moved nothing; it chose. Measured over nine pose sets, the docking engine put a pose within 2 Å of the crystal first once and this function did it four times, and on the run the engine got right it picked the same pose. Here the two agree, which is two independent functions on the same answer.

Boltz-2 scored pose 1 alone, before and after MD: see the affinity block in the Score panel. Running the affinity head on all 7 poses would cost about 42 minutes and is not done by default.

Run

ProteinP07550
Ligandcarazolol
Familygpcr
Reference2RH1 · CAU
TM-score, whole chain0.841
Pocket Ca atoms fitted53
Analysis43.6 s

Engine versions

gobsmacked_run1.0.0
python3.11.16
platformDarwin arm64
rdkit2026.03.1
openmm8.6
mdtraj1.11.1
torch2.10.0
pdbfixerinstalled
openmmforcefields0.16.0
pandadockv4.1.1

The receptor was co-folded with the ligand and the predicted ligand pose was then discarded, so docking starts from a pocket shaped around this ligand rather than an apo one. The discarded pose is in cofold/cofold_ligand.sdf.
The docking engine ranked its own pose 2 at position 2 of 9. A second scoring function (vinardo) placed it first, and it is the pose carried forward. Both sets of scores are in poses/, and the engine's original rank is a column in scores.csv.
The docking box was re-centred by 14.3 A during the run, from [5.73, -0.55, -7.13] to [2.64, 12.51, -2.27], to put it in the frame of the receptor this run built. The campaign recorded here is the one that ran.

Most displaced pocket side chains

Residue	Side-chain RMSD	chi1 model	chi1 crystal	difference
Trp313	3.06 A	-166.8	-83.3	83.5
Tyr316	2.42 A	-41.4	-71.7	30.3
Ile112	2.33 A	-165.9	-63.5	102.4
Ile309	2.31 A	-70.1	-72.6	2.5
Tyr308	2.19 A	174.7	-174.2	11.1
Tyr209	2.12 A	-84.6	-70.8	13.8
Ser203	2.09 A	64.0	-176.3	119.7
Phe290	1.98 A	-67.5	-77.7	10.2
Tyr174	1.95 A	66.3	75.4	9.1
Asn312	1.89 A	-162.3	-158.8	3.4

Interactions

Residue, 2RH1 numbering	MD final	Crystal
109	hydrophobic	hydrophobic
110	hydrophobic	—
113	hbond	hbond
114	hydrophobic	hydrophobic
117	hydrophobic	hydrophobic
193	hydrophobic	hydrophobic
199	—	hydrophobic
204	hbond	—
289	—	hydrophobic
290	hydrophobic	pi stacking
312	hbond	hbond
316	hbond	hbond

Residues are numbered as the crystal numbers them, because that is the only numbering both structures share. The PandaMap panel above uses the complex's own.
Jaccard overlap with the crystal: pose 1 0.357, MD final 0.538.

Interaction map

PandaMap's empirical estimate: -3.42 kcal/mol (Weak binder (Kd ~mM range)). Empirical estimate ±2–3 kcal/mol; not a substitute for FEP/MM-GBSA. Hover any residue or legend entry for what it means.

Mode: gpcr switches

Siteorthosteric
Receptor stateinactive-like
TM3-TM6 distance9.75 A vs 11.15 A
NPxxY RMSD1.86 A
Toggle switch chi1Trp286 -72.5
PIF motif8.07 A
Sodium site contact Asp79

Predictedorthosteric

Crystal 2RH1orthosteric

Binding mode matchesBoth the prediction and the crystal are orthosteric.

Dynamics

Report

A printable page with the scorecard, the mode verdict, the interaction table and the key traces. Printing preserves the panel colours.

Open report Download all