11. Docking

Question 1

Reasons for docking

Answer 1

• find molecule that exhibit a certain effect on target

- explain a proteins function by finding the native ligand

Question 2

Prerequisite for docking

Answer 2

Target structure
- target structure
- active site structure
Chemical database

Question 3

Druglikeness - Lipinski’s Rule of 5

Answer 3

No more than one!
• No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–
hydrogen bonds)
• Not more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)
• A molecular mass less than 500 daltons
• An octanol-water partition coefficient[5] log P not greater than 5

Question 4

• Divided into two parts

Answer 4

• Search algorithm

* Scoring algorithm

Question 5

• Commonly used models include

Answer 5

• Rigid body docking (mostly early docking algorithms and now only in protein protein docking)
• Fixed receptor – flexible ligand

• Grid potential based representation of protein- flexible ligand
– Most common today

• Fragment based methods

• De novo design methods
– Build molecules inside active site, more for later stages of projects

Question 6

Preparation of protein

Answer 6

• Assign borders of active site • Purple box
• Select starting point for ligands
• Red spheres
• Calculate potential maps for
active site
• The potential maps allow for a certain overlap of ligand and receptor and thus allows for some flexibility
• Protein is set for docking

Question 7

Protein – Protein Docking

Answer 7

• Protein-protein interactions play a central role in various aspects of the structural and functional organization of the cell
• Structures of complex are not always easily determined
• Paradox of Protein – protein docking
• Higher number of participating subunits grants a higher probability to predict the overall complex
structure

Question 8

Methodology prot-prot

Answer 8

• Commonly based on rigid body shape complementary supplemented by electrostatic calculations

Question 9

Prot-prot

• A development is the

Answer 9

Fast Fourier transformation algorithms that are becoming more common in newly developed software

Question 10

Docking enhanced with experimental data

Answer 10

• HADDOCK (High Ambiguity Driven protein–protein DOCKing)
• use of biochemical and/or biophysical interaction data such as
– chemical shift perturbation data resulting from NMR titration experiments
– mutagenesis data