December 2008 Newsletter

MolSoft Newsletter: December 2008 In this issue:

• End of Year Discount
• Next ICM Workshop: Protein Structure and Drug Design February 5th to 6th 2009
• 2009 ICM User Group Meeting: Challenges in Protein Structure Prediction and Drug Design
• New ICM Publication: Type-II Kinase Inhibitor Docking, Screening, and Profiling Using Modified Structures of Active Kinase States
• Floating ICM licenses for the Mac are now available.
• New Features in the latest ICM version 3.6-1d.
• ICM Power Tip: How to search for chemicals in very large databases.

End of Year Discount

We are offering a 20% discount on all ICM-Pro and MolCart products. This special end of year offer applies to new customers or current customers who wish to add additional licenses to their existing license agreement. Submit your purchase order before December 31st 2008 and receive a additional 20% discount on all our ICM-Pro molecular modeling and cheminformatics products.

Next ICM Workshop: Protein Structure and Drug Design February 5th to 6th 2009

The workshop will be conducted by: Prof. Ruben Abagyan (The Scripps Research Institute) and Dr. Maxim Totrov (Principal Scientist, MolSoft LLC). The workshop will consist of lectures, demonstrations, and "hands-on" computational experiments and cover the following topics:

• Sequence and Protein Structure Analysis
• Protein Modeling and Simulations
• Structure Validation and Optimization
• Ligand Binding Site Prediction
• Small Molecule Docking and Virtual Ligand Screening
• Structure-based development of target-specific compound libraries
• Cheminformatics, chemical clustering, searching, superposition ...
• QSAR, machine learning
• Protein-Protein Docking

A registration form can be downloaded here.

2009 ICM User Group Meeting: Challenges in Protein Structure Prediction and Drug Design

Please join us at our ICM User Group Meeting on April 9th and 10th to be held in La Jolla, CA. Come and hear about the latest developments in: Structure and Ligand Based Drug Design, Membrane Protein Modeling, Protein Structure Analysis, Virtual Ligand Screening, Protein-Protein Docking, Data Visualization, and Chemical Biology. The registration fee for Academics is $99 and for Commercial is $300. A registration form can be downloaded here.

New ICM Publication : Type-II Kinase Inhibitor Docking, Screening, and Profiling Using Modified Structures of Active Kinase States. Kufareva and Abagyan J. Med Chem

Download the paper here.

Abstract:Type-II kinase inhibitors represent a class of chemicals that trap their target kinases in an inactive, so-called DFG-out state, occupying a hydrophobic pocket adjacent to the ATP binding site. These compounds are often more specific than those that target active DFG-in kinase conformations. Unfortunately, the discovery of novel type-II scaffolds presents a considerable challenge, partially because the lack of compatible kinase structures makes structure-based methods inapplicable. We present a computational protocol for converting multiple available DFG-in structures of various kinases (?70% of mammalian structural kinome) into accurate and specific models of their type-II bound state. The models, described as deletion-of-loop Asp-Phe-Gly-in (DOLPHIN) kinase models, demonstrate exceptional performance in various inhibitor discovery applications, including compound pose prediction, screening, and in silico activity profiling. Given the abundance of the DFG-in structures, the presented approach opens possibilities for kinome-wide discovery of specific molecules targeting inactive kinase states.

Floating Licenses for the Mac

Due to customer demand we now offer floating licenses for the Mac platform. A floating license is placed on a server and any client computer connected to the server can “check out” the license. In the past all ICM licenses for Mac were locked to a particular machine (nodelocked license). The floating license option now gives you more flexibility in your ICM use if you need it. You can receive a floating license for Mac the next time you renew or purchase a new license.

New Features in the Latest ICM Version

The new ICM developments are listed in the Release Notes here. In particular please see:

• Lots of new developments in the ICM Ligand Editor
• New selections for Hbond donors and acceptors
• New table coloring options

ICM Power Tip: Chemical searching very large databases.

ICM tables are capable of storing tens of thousands records. However, some problems operate with data sets so large that they do not fit in computer's memory. To work with such large amounts of data ICM uses the concept of Molsoft database (MOLT) files. Unlike many other table file formats, such as SDF, CSV and others, database files are optimized for fast search and other operations, like unique entry addition and diverse subset selection. To learn how to make a MOLT file and search see here.