HOW DOCK WORKS

Step 1: Start with crystal coordinates of target receptor

In this example, HIV-1 protease is the target receptor, with its active site aspartyl groups identified in red.

Step 2: Generate molecular surface for receptor

This is performed using Mike Connolly's ms program. Note that only the surface for the active site needs to be generated.

For the rest of this overview, we'll use a a blow up of the active site.

Step 3: Generate spheres to fill the active site

The shape of cavities in the receptor is used to define spheres; the centers of the spheres become potential locations for ligand atoms.

In the following picture, the sphere centers are identified by cyan triangles, and the sphere surfaces are shown.

Side view of spheres:

DOCK

Step 4: Matching

Sphere centers are then matched to the ligand atoms, to determine possible orientations for the ligand. Typically on the order of tens of thousands of orientations are generated for each ligand molecule.

Step 5: Scoring

Each oriented molecule is then scored for fit. There are currently 3 scoring schemes:

Shape scoring, which uses a loose approximation to the Lennard-Jones potential
Electrostatic scoring, which uses the program DELPHI to calculate electrostatic potential
Force-field scoring, which uses the AMBER potential.

DOCK

This is the top-scoring orientation for the molecule thioketal in the HIV1-protease active site, using force-field scoring. (Please note that this is a different orientation than previously published. Earlier runs were done using the shape scoring scheme, and a different version of the protease crystal structure)

Final notes:

Here is a comparison of the top scoring orientation of the molecule thioketal with the orientation found in the crystal structure.

Rotating the view 90 degrees...

DOCK

All images on this page were produced with UCSF MidasPlus.

Please email questions or comments to Malin Young.