LigPrepVina applies three sequential filters. A 10% margin is applied to all thresholds to avoid rejecting borderline compounds.
① Lipinski's Rule of Five 10% margin
Evaluates whether a compound is likely to be orally active. Checks four physicochemical properties.
| Property | Standard Rule | LigPrepVina (10% margin) | What it means |
|---|
| Molecular Weight (MW) | ≤ 500 Da | ≤ 550 Da | Larger molecules are poorly absorbed |
| logP | ≤ 5 | ≤ 5.5 | High = poor water solubility |
| Hydrogen Bond Donors (HBD) | ≤ 5 | ≤ 6 | Too many = poor permeability |
| Hydrogen Bond Acceptors (HBA) | ≤ 10 | ≤ 11 | Too many = poor permeability |
Tolerance: Rejected only if 2+ rules violated. 1 violation = passes.
② ADMET Filter 10% margin
Checks oral bioavailability and absorption. Based on Veber's rules.
| Property | Standard Rule | LigPrepVina (10% margin) | What it means |
|---|
| Rotatable Bonds | ≤ 10 | ≤ 11 | Too many = poor bioavailability |
| TPSA | ≤ 140 Ų | ≤ 154 Ų | High = poor absorption |
| logP Range | -2 to 5 | -2.2 to 5.5 | Must not be too hydrophilic/lipophilic |
Tolerance: Rejected if any one check fails. All three must pass.
③ PAINS Filter no margin
Pan-Assay Interference Compounds — false positives in screening. Rejected if any PAINS substructure is found.
| PAINS Class | Example Pattern | Why it's problematic |
|---|
| Rhodanines | Thiazolidinedione with sulfur | Frequent false positive |
| Enones | Michael acceptors | React covalently with proteins |
| Catechols | 1,2-dihydroxybenzene | Redox-active, auto-oxidizes |
| Anils (imines) | C=N bonds | Unstable in assays |
Tolerance: Zero. A single PAINS alert = rejected.
How Filters Work Together
Input → Deduplication → Lipinski → ADMET → PAINS → Stereoisomers → PDBQT
- Filters applied sequentially — must pass each stage.
- Each filter can be toggled off from the upload interface.
- Lipinski: 1 violation allowed. ADMET: all must pass. PAINS: zero tolerance.