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

Recent ICM DevelopmentsNew Features in 3.6-1d versus 3.5-1r

109/17/2008 Copyright MolSoft LLC

Measures to Improve Version Independence and Stability

StandardICM version 3.5-1r

CurrentICM version 3.6-1c

Development VersionICM 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


BugZilla

09/17/2008 Copyright MolSoft LLC 3

New bug reporting website enables ICM developers to keep track and respond quickly to any bug report.

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.


ICM INTERACTIVE LIGAND EDITOR

Fully interactive environment for the design and optimization of small molecules in a receptor binding pocket.


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)


Ligand Editing (1)Modify Terminal Atom With

Chemical Group Add a Heavy Neighbor

Undo and Redo on all Edits


Ligand Editing (2)

Change Atom Property Change Bond Type


Ligand Editing (3)

Option to Edit in 2D Delete Atoms and Bonds


Docking and MinimizationRemove Clashes by Re-Docking

or Minimization Restrained Docking


Find Best Replacement GroupScreen A Database of

SubstituentsSubstituents Ranked by Score

One click visualization


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.


TABLES AND PLOTTINGNew table features and plotting options in ICM 3.6-1d versus 3.5-1r


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


Plotting ToolsNew plotting tools include:• Separate zooming for X and Y axiszooming 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)


Local DatabasesAdvantages: Allows you to view and search very large compound databases.

Some of the main features include:• Import SDF, CSV/TSV, ICM tablesSearch (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


Focused Markush Library Docking


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.

MOLECULAR GRAPHICS AND VISUALIZATION

View ICM interactively in PowerPoint and Web, new graphics options… 3.6-1d versus 3.5-1r


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


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.


New Display StylesControl of Chain Break

Visualization at Molecular Level Smooth Ribbon


Ligand and Receptor Hydrogen Option

Background Image


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.


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

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