CADD: An Introduction to Computer-Aided Drug Design

What is CADD?

Computer-Aided Drug Design (CADD) uses computational methods to identify, optimise, and prioritise drug candidates before expensive wet-lab experiments. It dramatically reduces the time and cost of the early-discovery pipeline.

Two Main Approaches

Structure-Based Drug Design (SBDD)

Relies on a known 3-D structure of the biological target (protein, nucleic acid) obtained by X-ray crystallography, cryo-EM, or NMR.

Key workflows:

• Molecular docking (AutoDock Vina, Glide, GOLD)
• Molecular dynamics (MD) simulation (GROMACS, AMBER, NAMD)
• Free-energy perturbation (FEP) calculations

Ligand-Based Drug Design (LBDD)

Used when no target structure is available. Works from a set of known active and inactive molecules.

Key workflows:

• QSAR / QSPR modelling
• Pharmacophore modelling (Phase, LigandScout)
• Similarity searching and scaffold hopping

Standard CADD Pipeline

Target ID ? Protein Prep ? Active Site Analysis
    ? Virtual Screening ? Hit Selection
        ? Lead Optimisation ? ADMET Prediction

Popular Software

Why CADD Matters

CADD has contributed to approved drugs such as HIV protease inhibitors and influenza neuraminidase inhibitors, demonstrating its real-world impact on medicine.