target-based-lead-design

Target-Based Lead Design

Generate diverse, drug-like lead compounds targeting a specific protein using AI-powered structure-based drug design.

When to Use

• User provides a PDB ID or disease name and wants drug candidates
• User wants to design molecules for a specific protein target
• User needs diverse leads with user-defined property criteria
• User wants iterative refinement with regeneration loop

Inputs

User Criteria (Filtering Thresholds)

Workflow

Phase 1: Target Identification
    └── Path A: PDB ID provided → Download structure directly
    └── Path B: Disease/target name provided → Agent-based discovery:
           ├── Agent searches web for PDB structures
           ├── Agent examines each PDB's ligands
           ├── Agent searches literature to validate ligand is a true binder
           │      └── Fallback (if 3 search attempts fail):
           │             └── Judge by molecular weight:
           │                    • MW ≥ 150 Da → Likely drug-like binder (accept)
           │                    • MW 100-150 Da → Fragment (accept with caution)
           │                    • MW < 100 Da → Likely solvent/ion (exclude)
           ├── Agent ranks by resolution, returns best PDB ID
           └── If no valid PDB found → Ask user for PDB ID

Phase 2: Structure Preparation
    └── Extract protein chains and ligands
    └── Define binding pocket (from reference ligand)

Phase 3: De Novo Generation
    └── Generate candidates using MolCraft
    └── Save candidates to SDF files

Phase 4: Docking
    └── Dock all candidates (AutoDock Vina)

Phase 5: Property + ADMET Calculation
    └── Drug-likeness: QED, SA, LogP, Lipinski
    └── ADMET: BBB penetration, Side effects (SIDER)

Phase 6: Filtering & Diversity Selection
    └── Apply user criteria → Filter candidates
    └── Greedy diversity selection (Tanimoto)
    └── Regeneration check → Iterate if needed

Phase 7: PLIP Interaction Analysis (selected molecules only)
    └── Analyze protein-ligand interactions for selected leads
    └── Report hydrophobic contacts, H-bonds, π-stacking, salt bridges

Phase 8: Visualization (selected molecules only)
    └── 2D molecule structures (RDKit)
    └── 3D rotating complex GIF (PyMOL, requires installation)