Frequent Questions & Answers

What is Molecular Docking?

In general, "docking" is the identification of the low-energy binding modes of a small molecule, or ligand, within the active site of a macromolecule, or receptor, whose structure is known. A compound that interacts strongly with, or binds, a receptor associated with a disease may inhibit its function and thus act as a drug. Solving the docking problem computationally requires an accurate representation of the molecular energetics as well as an efficient algorithm to search the potential binding modes.

How does Molecular Docking work?

A typical DOCK setup used toward the discovery of a potential disease inhibitor is presented below. The target is usually a protein or active site of RNA. 1. Add proton, VDW parameters, and partial charges for both target and small molecule. 2. Calculate solvent accessible surface area of target. 3. Create negative image of surface features surrounding active site using spheres. 4. Calculate energy grid for target. Each grid point stores VDW score and charge for that area of space. 5. Match ligand atoms to sphere centers and score against grid. 6. Rank best scoring poses or ranked by their potential to bind to the target.

What is Computational Molecular Docking?

Computational molecular docking is a research technique for predicting whether one molecule will bind to another, usually a protein. Protein-protein, protein-DNA and protein-ligand docking predictions are all performed, though the techniques employed in each area are highly various. Protein-ligand docking is done by modeling the interaction between protein and ligand: if the geometry of the pair is complementary and involves favorable biochemical interactions, the ligand will potentially bind the protein in vitro or in vivo.

Why Use Computational Molecular Docking?

A binding interaction may mean that the ligand inhibits the protein's function or acts as an agonist. Docking is most pertinent to the field of drug design—most drugs are small molecules, and using a computational approach allows researchers to quickly screen large databases of potential drugs.

We and others have used DOCK for the following applications:

• predict binding modes of small molecule-protein complexes
• search databases of ligands for compounds that inhibit enzyme activity
• search databases of ligands for compounds that bind a particular protein
• search databases of ligands for compounds that bind nucleic acid targets
• examine possible binding orientations of protein-protein and protein-DNA complexes
• help guide synthetic efforts by examining small molecules that are computationally derivatized
• many more...

What are the Examples of New Drugs Developed through Docking Technology?

• ARX-201, long acting HGH, growth deficiency, preclinical
• Mozobil, blocks CRCR4, lymphoma leukemia, phase III
• AG-ME-0040, peptide molecule activates, anemia, preclinical
• Angiomax, anticoagular, bypass patients, marketed
• ILPIP, Antiapoptotic protein, cancer treatment, preclinical
• AT7519, cell cycle inhibitor, cancer treatment, phase II
• ABS201, peptide derivative, schizophrenia, preclinical
• PTEN, restore tumor suppress, cancer treatment
• XIAP, inhibitor of apoptosis, cancer treatment
• DR1501, blocking binding to MBP, treatment of multiple sclerosis
• many more...

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