Introduction

In this example we are going to look at the effect of an agonist binding to the Beta-2-Adrenergic GPCR (B2AR) and prepare a molecular document. A prepared ICM file containing three B2AR GPCRs superimposed can be downloaded here ftp://ftp.molsoft.com/pub/workshop/ (1. cut and paste the address into a web browser. 2. Right click on GPCR_slides.icb and choose "Save Link As". 3. Open the .icb in ICM File/Open). The file contains pdb files 2RH1 (R inactive state), 3P0G (R* active state, with G-alpha mimic), and 3SN6 (R*G G-protein signalling state). The agonist ligand causes Helix 5 to shift inwards and Helix 6 to swing outwards. This agonist binding poses were predicted using ICM a year before the crystal structures were solved, you can read about this here and a good review of the structure and function of GPCRs here.

Tutorial

Step 1: Download the example file here ftp://ftp.molsoft.com/pub/workshop/ (1. cut and paste the address into a web browser. 2. Right click on GPCR_slides.icb and choose "Save Link As". 3. Open the .icb in ICM File/Open). Make a slide by clicking on the camera button at the bottom of the GUI.

Step 2: The slide is stored in the ICM Workspace panel (left hand side of the GUI). You can make changes to the 3D display and return to the display in the slide by clikcing on the slide in the ICM Workspace.

Step 3: Properies of the slide can be edited by right clicking on the slide in the ICM workspace.

Step 4: Saving a viewpoint is useful if you are making many slides from the same viewing position.

Step 5: In this slide we show that Helix 5 makes an inward shift when an agonist binds.

Step 6: In this slide we show that upon binding an agonist Ile121 switches its rotameric state and Phe 282 moves.

Step 7: In this slide we show that agonist binding causes Helix 6 to swing out.

Step 8: You can export the slides as a movie or you can browse through them using the arrow buttons.

Step 9: To build a molecular document you can annotate the slides using HTML.

Step 10: Edit the document by right clicking on the HTML panel and choosing Edit.

Step 11: Hyperlinks can be made to the slide. Other functions such as adding check boxes, ICM scripts and external links are also available.

Step 12: Save the molecular document in icb format and view in ICM-Pro or ICM-Browser. You can also export to a web browser or view the fully interactive slides in Windows Powerpoint using a plugin called ActiveICM.