Paramus — Docking Pose Screen

Overview

Prepare ligands and target, dock, and rank poses by predicted binding + interaction quality. The value is the prepare→dock→rank→interpret loop with binding-plausibility judgment, not a raw score.

Guidance vs execution: docking runs on a tested Paramus engine with provenance. Do not hand-run a docking script — route to the engine.

When to Use

• Rank a candidate set for binding to a defined target/pocket
• Triage virtual-screening hits before assay Do not use for: free-energy perturbation / MD-grade affinity (hand off to the FEP/MD workflow).

Workflow

Ligand set + target structure (+ pocket / co-crystal reference)
  ↓ 1. Prepare ligands              → protonation, tautomers, 3D embed
  ↓ 2. Prepare receptor & pocket    → Paramus structure prep tool
  ↓ 3. Dock                         → Paramus docking engine
  ↓ 4. Score & analyze interactions → H-bonds, hydrophobic, clashes
  ↓ 5. Rank & report                → ranked poses + interactions + provenance

Procedure

1. Discover tools via search/get_schema ("ligand preparation", "molecular docking", "binding pocket").
2. Prepare ligands (protonation/tautomers/3D); report any that fail.
3. Prepare receptor and define the pocket (from reference ligand or coordinates).
4. Dock the set on the Paramus engine; capture scores + poses + engine version.
5. Analyze interactions; flag poses with clashes or implausible geometry.
6. Rank by score gated on interaction quality; report top poses with rationale.

Domain Judgment

• Docking score is a ranking device, not an affinity — never report it as Kd/IC50.
• A high score with poor interactions/clashes is a red flag, not a winner.
• Consistent preparation and engine version across the set, or the ranking is meaningless.

Fallbacks

• Docking engine unavailable → report; offer a pharmacophore/similarity pre-filter instead.
• Endpoint unreachable → stop and report; no local docking fallback.