1. Recent ICM Developments New Features in 3.6-1d versus 3.5-1r 109/17/2008 Copyright MolSoft LLC

2. Measures to Improve Version Independence and Stability Standard ICM version 3.5-1r Current ICM version 3.6-1c Development Version ICM version 3.7 Introduced 3 new ICM versions to address the concurrent use of 3 widely spanning distributions Separated the Standard version into a different cvs repositories Added bee libraries, macros, scripts, and docs to be consistent with the version Banned direct posting of updated versions Introduced internal review and censorship for new features Expanded the tools for automated testing and expanded the set of tests Standardized and expanded the interactive human testing process 209/17/2008 Copyright MolSoft LLC

3. BugZilla 09/17/2008 Copyright MolSoft LLC3 New bug reporting website enables ICM developers to keep track and respond quickly to any bug report.

4. Improved Documentation We performed an overhaul of the documentation Expanded the keyword search Added a Google search option Separated manuals from different versions into different repositories. It allowed to keep the images consistent with the current interface. Documented essential macros Documented the GUI language and the 'make plot' language that were considered as internal languages previously. 409/17/2008 Copyright MolSoft LLC

5. ICM INTERACTIVE LIGAND EDITOR Fully interactive environment for the design and optimization of small molecules in a receptor binding pocket. 509/17/2008 Copyright MolSoft LLC

6. Ligand-Receptor Interactions Display Display pocket surface colored by property. White=neutral surface Green=hydrophobic surface Red=hydrogen bonding acceptor potential Blue=hydrogen bond donor potential Display atomic energy rings colored green to red. Orange/Red Stars represents a clash Display hydrogen bonds. New selections a_Rec. (receptor), a_.I (Inhibitor/ligand), a_.T (templates), a_./R (rotatable residues), a_./L (ligand pocket residues) 609/17/2008 Copyright MolSoft LLC

7. Ligand Editing (1) Modify Terminal Atom With Chemical Group Add a Heavy Neighbor Undo and Redo on all Edits 709/17/2008 Copyright MolSoft LLC

8. Ligand Editing (2) Change Atom PropertyChange Bond Type 809/17/2008 Copyright MolSoft LLC

9. Ligand Editing (3) Option to Edit in 2DDelete Atoms and Bonds 909/17/2008 Copyright MolSoft LLC

10. Docking and Minimization Remove Clashes by Re-Docking or Minimization Restrained Docking 1009/17/2008 Copyright MolSoft LLC

11. Find Best Replacement Group Screen A Database of Substituents Substituents Ranked by Score One click visualization 1109/17/2008 Copyright MolSoft LLC

12. Fragment Docking and Linking Generate ligand fragments from known leads. Dock fragment molecules into binding site. Sample a variety of linker molecules between selected fragments. 1209/17/2008 Copyright MolSoft LLC

13. TABLES AND PLOTTING New table features and plotting options in ICM 3.6-1d versus 3.5-1r 09/17/2008 Copyright MolSoft LLC13

14. New Table Features Freeze column option (Microsoft Excel Style) Text wrapping for long column names by underscore Support for ND values Number of unique alternatives in the column filters is not limited anymore New short view for a table with families of rows (set group column command) Added a way to join one column from one table to another table. Ability to store and re-apply "table views" (filters + hidden columns) Ability to save tables as database files Change column background color Export chemical spreadsheets and tables directly to Microsoft Excel Introduction of dependent and automatically updateable columns 1409/17/2008 Copyright MolSoft LLC

15. Plotting Tools New plotting tools include: Separate zooming for X and Y axis zooming into/out of a certain point on the plot, wheel zoom Axis customization: setting titles and steps Point labels in scatter plots, showing labels for selection only Interactive control over histogram bin size to allow finding the best density estimation picture Added horizontal bars Logarithmic scales – working now New scatter plot styles: connected, bars and triangles New matrix plot (used in interactive Ramachandran plots) 1509/17/2008 Copyright MolSoft LLC

16. Local Databases Advantages: Allows you to view and search very large compound databases. Some of the main features include: Import SDF, CSV/TSV, ICM tables Search (chemical) Manage databases: rename/delete tables. Clustering (selecting a representative set) Select diverse set (distance cutoff feature) Editing (deleting/inserting/modifying) Add columns and append tables Full text search support Unique field support Export SDF, CSV/TSV 1609/17/2008 Copyright MolSoft LLC

17. Focused Markush Library Docking 09/17/2008 Copyright MolSoft LLC17 A more efficient approach to docking a Markush library is not to dock the whole library but to generate a FOCUSED Markush Library and dock. Step 1: Draw the Markush scaffold and enumerate a library with defined R1, R2 … groups Step 2: Explore one R group at a time during docking. Step 3: Make a Hitlist and use the top hits to generate a FOCUSED Markush library Step4: Dock FOCUSED Markush library and evaluate the results.

18. MOLECULAR GRAPHICS AND VISUALIZATION View ICM interactively in PowerPoint and Web, new graphics options… 3.6-1d versus 3.5-1r 1809/17/2008 Copyright MolSoft LLC

19. ActiveICM ActiveICM (Patent Pending) enables you to view and display 3D ICM graphical slides and animations interactively inside Microsoft PowerPoint and web browsers such as Internet Explorer and Mozilla Firefox. Download free from www.molsoft.com/support 1909/17/2008 Copyright MolSoft LLC

20. Occlusion Shading The procedure calculates for each surface element (triangle) the extent it is occluded from ambient light by other parts of the molecule, and makes the elements darker proportionally to occlusion. Thus, concave regions such as pockets become dark since the surrounding bulk of the protein blocks the light from most directions, while protrusions remain bright since they are well exposed. 2009/17/2008 Copyright MolSoft LLC

21. New Display Styles Control of Chain Break Visualization at Molecular Level Smooth Ribbon 09/17/2008 Copyright MolSoft LLC21 Ligand and Receptor Hydrogen Option

22. Background Image 2209/17/2008 Copyright MolSoft LLC

23. New 3D Object Support Render and display any 3D object in ICM. e.g. KMZ and COLLADA format directly from the Google Sketchup website. Microsoft Virtual Earth uses this file format as well as CAD software companies such as Dassault Systems. We have also added options for changing the texture and material of a 3D object. 3D XML file format which is a popular 3D format for CAD. 2309/17/2008 Copyright MolSoft LLC