1. Macromolecular Structural Repositories

Selecting the ideal structural model for your drug target is the single most critical determinant of docking accuracy.

• RCSB Protein Data Bank (PDB): The global open repository of experimental 3D structures determined by X-ray crystallography, cryo-EM, and NMR. When selecting a PDB code, prioritize:
  • High crystallographic resolution ($\le 2.2\text{ \AA}$ for X-ray; $\le 3.0\text{ \AA}$ for cryo-EM).
  • Low $R_{\text{free}}$ and $R_{\text{work}}$ metrics ($\le 0.25$).
  • Structures co-crystallized with a relevant pharmacophore ligand (holo-state) to guarantee an open, induced binding cavity.
• AlphaFold Protein Structure Database (EMBL-EBI): Contains $>200$ million AI-predicted protein structures covering almost all known organisms. Best utilized when experimental crystals are unavailable.
• UniProtKB: Primary resource for protein sequence annotation, domain boundaries, catalytic residue numbers, and disease-associated missense variants.

2. Chemical Databases for Virtual Screening

import urllib.request
import json

# 1. Download PDB structure directly from RCSB
pdb_id = "6LU7" # SARS-CoV-2 Main Protease
rcsb_url = f"https://files.rcsb.org/download/{pdb_id}.pdb"
urllib.request.urlretrieve(rcsb_url, f"{pdb_id}.pdb")
print(f"Downloaded {pdb_id}.pdb from RCSB PDB")

# 2. Query PubChem PUG-REST API for a known antiviral inhibitor
compound_name = "nirmatrelvir"
pug_url = f"https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/{compound_name}/SDF?record_type=3d"
urllib.request.urlretrieve(pug_url, f"{compound_name}_3d.sdf")
print(f"Downloaded 3D SDF for {compound_name} from PubChem")