Phase 1 – Drug Design & Molecular Docking
Phase 1 – Drug Design & Molecular Docking contains 18 topic pages in Pharmaceutical Chemistry.
Learning Objectives
- Distinguish rational, structure-based, ligand-based, and computational drug design approaches.
- Describe the complete molecular docking workflow from protein retrieval to results interpretation.
- Explain how binding energy, RMSD, and non-covalent interactions are used to interpret docking results.
- Describe pharmacophore modelling and virtual screening as hit-identification strategies.
- Explain the role of molecular dynamics simulation in validating docking predictions.
- Describe emerging computational approaches including AI-guided design, PROTACs, and fragment-based design.
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Topics and Topic Groups
Browse the available learning units in this chapter.
Rational Drug Design
Rational drug design is the hypothesis-driven approach to compound design in which chemical structures are proposed on the basis of a defined understanding...
Structure-Based Drug Design (SBDD)
Structure-based drug design uses the experimentally determined or computationally predicted three-dimensional structure of a target protein, typically...
Ligand-Based Drug Design (LBDD)
Ligand-based drug design is applied when the three-dimensional structure of the target is unavailable or unreliable, and instead derives design hypotheses...
Computational Drug Design (CADD)
Computer-Aided Drug Design encompasses the full suite of computational methods — molecular docking, molecular dynamics simulation, pharmacophore modelling,...
Protein Structure Retrieval (PDB)
The first practical step of any structure-based design or docking exercise is retrieval of an appropriate three-dimensional target structure, most commonly...
Protein Preparation
Protein preparation converts a raw, as-deposited PDB structure into a chemically and geometrically valid model suitable for docking calculations, correcting...
Active Site Identification
Active site identification defines the specific three-dimensional region of the target protein within which docking calculations will be performed, most...
Grid Box Generation
Grid box generation defines the three-dimensional spatial region within which the docking search algorithm will explore candidate ligand poses, centred on...
Ligand Preparation
Ligand preparation converts the two-dimensional chemical structure of each candidate compound into an energetically reasonable, correctly protonated, and...
Molecular Docking
Introduction and Principle Molecular docking is a computational technique that predicts the preferred binding orientation, or pose, of a small molecule...
Docking Score Interpretation
The numerical docking score generated by a docking calculation provides a relative, rather than absolute, estimate of predicted binding affinity, and should...
RMSD (Root-Mean-Square Deviation)
Root-mean-square deviation quantifies the average positional difference, typically measured in Ångströms, between two superimposed sets of atomic...
Binding Energy
Binding (or free) energy quantifies the thermodynamic favourability of the interaction between a ligand and its target, and can be estimated computationally...
Hydrogen Bond, Hydrophobic, and Electrostatic Interactions
The predicted binding pose generated by a docking calculation is conventionally analysed in terms of the specific non-covalent interactions formed between...
Pharmacophore Modelling
A pharmacophore is the abstract, three-dimensional arrangement of chemical features — hydrogen-bond donors and acceptors, hydrophobic centres, aromatic ring...
Virtual Screening
Virtual screening is the systematic computational evaluation of large compound libraries — commonly ranging from hundreds of thousands to tens of millions...
Molecular Dynamics
Molecular dynamics simulation computes the time-dependent physical motion of every atom within a molecular system — typically a ligand-protein complex,...
ADMET Prediction (Computational)
Computational ADMET prediction applies in-silico models — ranging from simple rule-based filters such as Lipinski's Rule of Five to sophisticated...