practicum 2 - M. Sc. Chemistry UAB

In this tutorial, you will be introduced the docking approaches by  ndertaking on your own some docking experiments on the androgen binding receptor seen in the tutorial I.  To do so, we will us Autodock, a flexible ligand-protein docking program which basically runs as a two steps procedure: the calculation of the map of interactions of the binding site with some general atom types (performed with autogrid) and the posing of the lligand respecting this map of interaction (performed with autodock).
Some of the  algorithms detailed during the  theoretical courses are available in Autodock. The actual version of the program  (the version we will use here) is the version 4.0 which provides with important new features for docking prospect like protein residue flexibility and high quality scoring functions. In reality we will use the vina version of the program that has been released about two years ago and that has been optimized to rapidely perfom otherwise complicated tasks with Autodock. We will also use the novel interface incorporated in UCSF chimera to carry out the work.

The different steps for the initial study as well as the possible extension of the work are summarize below.
1. Ligand and Protein Set up
Autodock scoring function is applied using an adapted AMBER force field therefore the atoms of the protein and the ligand have to be set up in accordance with  this ff. You first have to generate the files you need for the docking: a receptor structure and a ligand structure. Open the 2ama structure in chimera. Then keep a mol2 file for the steroid on one side and the receptor on the other. Close the session. Open back the structures one by one. Add the hydrogen to each structure (command line: addh).

3.Setting up the docking
Go to the Tools-->Surface/Binding Analysis --> Autodock Vina

There you have to enter all the minimal information needed to proceed with the calculations:

- Output file: where the output will be located

- Receptor: select the receptor model you want for receptor

- Ligand: the same but for the ligand

This done, you need to define the location of the space for the prediction of the binding (binding site). To do so, check the resize search volume using (whatever the button is). Then play with the center button to generate the right size of the box.

Do not touch everything else and send the calculation.

4. Analysis
Once the calculation has finished we can analysis the conformations obtained and their energy.  The output will pop up. That's your turn to do the analysis and check to which point the prediction is adequate.

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