FAIRMol

MK219

Pose ID 7689 Compound 2490 Pose 237

DB SELECTIONDocking pose analysis is being read from this database.
Molecular metrics status: done
RDKit SASA-based burial metrics are cached.
SASA cached
T12
T. brucei R5P T. brucei
Ligand MK219
PDB6FXS

3D complex viewer

Strict H-bonds Permissive H-bonds
Viewer legend
Protein receptor
Pocket residues
Cofactor context
Docked ligand
Overall assessment
Weak SASA cached
Promising but geometrically suspicious
Binding strong Geometry low Native strong SASA done
Strain ΔE
24.6 kcal/mol
Protein clashes
0
Internal clashes
13
Native overlap
contact recall 1.00, Jaccard 0.89, H-bond role recall 0.30
Burial
65%
Hydrophobic fit
80%
Reason: 13 internal clashes
13 intramolecular clashes 60% of hydrophobic surface is solvent-exposed (15/25 atoms). Large non-polar area without protein contacts incurs a desolvation penalty and will reduce binding affinity. Consider truncating or replacing the exposed fragment.
Molecular report
Full metrics ↗
Weak Marginal quality. Consider only alongside better-scoring alternatives.
✓ Excellent LE (-0.767 kcal/mol/HA) ✓ Good fit quality (FQ -7.54) ✓ Strong H-bond network (10 bonds) ✓ Good burial (65% SASA buried) ✓ Lipophilic contacts well-matched (80%) ✗ High strain energy (24.6 kcal/mol) ✗ Geometry warnings ✗ Many internal clashes (13)
Score
-24.545
kcal/mol
LE
-0.767
kcal/mol/HA
Fit Quality
-7.54
FQ (Leeson)
HAC
32
heavy atoms
MW
438
Da
LogP
4.28
cLogP
Strain ΔE
24.6 kcal/mol
SASA buried
65%
Lipo contact
80% BSA apolar/total
SASA unbound
750 Ų
Apolar buried
386 Ų

Interaction summary

HB 10 HY 10 PI 4 CLASH 0 ⚠ Exposure 60%
🚨Solvent-exposed hydrophobic surface — desolvation penalty likely
60% of hydrophobic surface is solvent-exposed (15/25 atoms). Large non-polar area without protein contacts incurs a desolvation penalty and will reduce binding affinity. Consider truncating or replacing the exposed fragment.
Non-polar atoms 25 Buried (contacted) 10 Exposed 15 LogP 4.28 H-bonds 10
Exposed fragments: phenyl (6/6 atoms exposed)phenyl (5/6 atoms exposed)aliphatic chain/group (6 atoms exposed)
Final rank3.490Score-24.545
Inter norm-1.025Intra norm0.258
Top1000noExcludedno
Contacts18H-bonds10
Artifact reasongeometry warning; 13 clashes; 2 protein clashes; moderate strain Δ 24.6
Residues
ARG140 ARG144 ASN106 GLU138 HIS105 HIS141 ARG46 ASP13 CYS72 GLY73 GLY75 GLY77 HIS14 ILE15 ILE76 MET78 SER74 TYR49

Protein summary

302 residues
Protein targetT12Atoms4598
Residues302Chains2
Residue summaryARG:576; ILE:456; VAL:448; GLU:360; ALA:340; LEU:304; TYR:252; HIS:204; PRO:196; THR:196; GLY:182; LYS:176; ASP:168; PHE:160; MET:153; SER:121

Receptor context

1 kept / 0 excluded
Receptor context filtering: interactions and SASA are computed against protein atoms plus allowed cofactors/ions. Native ligand-like HETATM partners are excluded from scoring.
Kept context 1 Excluded HETATM 0
Kept cofactors / ions
A:CSD72

Native ligand reference

★ reference
Interaction fingerprint calculated directly from the uploaded native ligand without docking. Current H-bond mode: strict.
Name6FXSContacts16
PoseOpen native poseHB0
IFP residues
ARG140 ARG144 ASN106 HIS105 HIS141 ARG46 ASP13 CYS72 GLY73 GLY75 GLY77 HIS14 ILE15 ILE76 SER74 TYR49
Current overlap16Native recall1.00
Jaccard0.89RMSD-
HB strict3Strict recall0.25
HB same residue+role3HB role recall0.30
HB same residue4HB residue recall0.40

HB · H-bonds

Mode: strict. Count shows atom-level H-bonds; unique residues in summary: 0.

PI · π–π interactions

Native π–π recall is disabled because no explicit native π–π reference was stored.

HY · Hydrophobic contacts

CLASH · Clashes

No clash · clashes detected for this pose.

All stored poses for this docking hit

PoseFinal rankInter normScoreHBCTCT overlapCT recallHB role rec.RMSDExcluded
260 1.1082347513979987 -0.775134 -20.4397 3 20 0 0.00 0.00 - no Open
248 2.4599060132209662 -0.840741 -20.296 7 18 0 0.00 0.00 - no Open
289 2.81667322176217 -0.671287 -17.9163 7 16 0 0.00 0.00 - no Open
289 3.2353618255927503 -0.939527 -26.2086 16 15 0 0.00 0.00 - no Open
237 3.4895145128219167 -1.02523 -24.5452 10 18 16 1.00 0.30 - no Current
320 3.5497150933488077 -0.655457 -19.1227 7 11 0 0.00 0.00 - no Open
210 4.017419003236659 -0.919734 -21.9628 10 18 0 0.00 0.00 - no Open
393 5.7079837755049425 -0.760916 -19.7213 10 14 0 0.00 0.00 - no Open

Molecular metrics

RDKit SASA burial, strain energy (MMFF94s), ligand efficiency and fit quality for this docking pose.
✓ Metrics available

Scoring & efficiency

Docking score -24.545kcal/mol
Ligand efficiency (LE) -0.7670kcal/mol/HA
Score / heavy atom count
Fit quality (FQ) -7.543
LE / (0.072 + 0.95/HAC) — Leeson & Springthorpe
Heavy atom count 32HA

Physicochemical properties

Molecular weight 437.5Da
Lipinski: ≤ 500 Da
LogP (cLogP) 4.28
Lipinski: ≤ 5
Rotatable bonds 9

Conformational strain (MMFF94s)

Strain energy (ΔE) 24.61kcal/mol
< 5 good · 5–10 marginal · > 10 problematic
Docked FF energy 57.31kcal/mol
Minimised FF energy 32.70kcal/mol

SASA & burial

✓ computed
SASA (unbound) 749.9Ų
Total solvent-accessible surface area of free ligand
BSA total 485.4Ų
Buried surface area upon binding
BSA apolar 386.0Ų
Hydrophobic contacts buried
BSA polar 99.3Ų
Polar contacts buried
Fraction buried 64.7%
> 60 % indicates good pocket engagement
Lipophilic contact ratio 79.5%
BSA apolar / BSA total — high = hydrophobic driver
Δ Non-polar SASA -2298.0Ų
SASA_nonpolar(complex) − SASA_nonpolar(receptor) − SASA_nonpolar(ligand free). Negative = non-polar surface buried upon binding. Requires full polarity-decomposed SASA computation.
Receptor non-polar SASA 2454.8Ų
Non-polar SASA of receptor alone (VdW proxy, nonpolar atoms only)
Complex non-polar SASA 787.2Ų
Non-polar SASA of full complex (VdW proxy, nonpolar atoms only)