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2009
12.23.2009: End of Year UpdateWe hope you all have a Merry Christmas and a Happy New Year. Thank you for your continued support. Below we have some end of year ICM news and a round up of some of our 2009 success stories.MolSoft in the MediaLast month the San Diego Union Tribune wrote an article about MolSoft - you can read the article online here. In July the American Chemical Society publication Chemical and Engineering News also reported on our ICM 3D Ligand Editor. There was also a lot of interest by blog writers and other media outlets about MolSoft's ActiveICM being used by PLoS ONE and SGC scientists for the publication of fully interactive 3D scientific papers. SGC scientists refer to ActiveICM as iSee and they have summarized all the media interest in this development here in the whatisisee wiki.Upcoming WorkshopsThis year we held two sold out ICM workshops and an ICM User Group Meeting. The User Group meeting was a fun and scientifically rewarding experience. You can see some of the photos from the User Group Meeting here (Photos by Dr. Lars Brive - Goteburg). Please join us in 2010 at one of our 2010 workshops including an ICM Scripting Workshop in January - places are filling up quickly so please register as soon as possible.
Bringing Online Publications to LifeAs mentioned earlier one of the big events this year was the exciting use of ActiveICM in the PLoS ONE journal to display fully interactive 3D objects. For the first time fully interactive 3D molecules were embedded in a peer-reviewed collection of research papers due to a collaboration with scientists at the SGC in Oxford UK. You can see the full PLoS ONE collection on their website. You can use ActiveICM for free and download it from here.Lots of New Cheminformatics FeaturesDuring the past year the number of chemistry related features inlcuded in ICM has grown significantly. We now have two chemistry products ICM-Chemist and ICM-Chemist-Pro. ICM-Chemist is ideal for all 2D chemical operations including sketching, editing, clustering and database enumeration. ICM-Chemist-Pro includes all the tools in ICM-Chemist plus 3D options such as chemical superposition and our popular 3D ligand editor. If you would like to try these products please let us know and we can send you an evaluation license.New ICM-Chemist Tutorials Including VideosPlease check out the new series of ICM-Chemist tutorials including online videos. If you have ICM-Chemist or ICM-Pro-VLS then you have all the features described in these tutorials. More tutorials in this format will be released early next year so we would welcome your feedback.Holiday Reading! Some Selected 2009 ICM Success Stories
10.20.2009: MolSoft's New Technology Brings Online Publications to Life in Fully Interactive 3D.
Scientific publishing is now going 3D. For the first time in online publishing history, the PLoS ONE journal is publishing original research papers containing fully annotated and interactive 3D objects. This 3D environment provides a "movie-like" experience but with a significant difference - the reader is in control of the scenes and each view is linked directly to the text. This is possible because of a new technology called ActiveICM developed by MolSoft LLC. ActiveICM is now being used for scientific publishing due to a collaboration with scientists at the SGC. Initially the technology is being applied to the life sciences for the 3D display of the atomic structures of molecules implicated in disease. ActiveICM can also be used for any online publication where a 3D view would enhance the subject matter. Click here to see the PLoS ONE collection of papers. Click here to read the press release.
10.08.2009: New MAC version of MolSoft's ICM Desktop Modeling Software is Now Available Please visit our support site to download the latest MAC version 3.7-1f of ICM-Browser, ICM-Browser-Pro, ICM-Chemist and ICM.
10.07.2009: MolCart Building Blocks Database for Combinatorial Chemistry has been Updated Click to enlarge image.
The MolCart Building Block database has been updated. The database consists of chemical building blocks for combinatorial chemistry from 32 different chemical vendors and contains 4,408,865 non-redundant chemical fragments. The database contains a wide variety of scaffolds which can be used to generate libraries using Molsoft's combinatorial library tools contained in ICM-Chemist. ICM-Chemist contains a large selection of tools for chemical enumeration and decomposition. You can create or modify a Markush structure and enumerate a library on the fly by adding chemical fragments to defined "R-groups". You can also enumerate by chemical reaction and decompose a database into chemical fragments.
9.22.2009: A new 64-Bit Beta Version of ICM is now availableA new 64-bit Beta version of ICM is available. Please contact andyATmolsoft.com if you would like to try this version of ICM.
9.19.2009: ICM Graphics On Front Cover of New Book on Chemogenomics Click to enlarge image.
ICM graphics is featured on the front cover of a new book edited by Edgar Jacoby (Novartis) on Chemogenomics. More information about the book can be found here. The image is of the contoured electron density of a ligand. Click here for instructions on how to contour electron density in ICM.
7.22.2009: Updated MolCart Compound Database Click to enlarge image.
The Molcart Compound Screening Database has been updated. The database is a collection of compounds from 33 chemical vendors who let us know whenever a new set of compounds is added or removed from their database.The database currently contains 8,275,223 compounds and the total number of redundant compounds is 4,474,597. The latest changes to the database are documented here. One of the advantages of the MolCart Compound Screening Database is that we take great care to ensure the compounds that are listed are actually available for purchase. Other compound database collections list compounds that are virtual and in theory can be synthesized but they are expensive and are rarely available for quick purchase. If you are a MolCart customer please update your database collection by clicking here and download individual vendor databases or our non-redundant compilation. If you are interested in purchasing MolCart you can get a 2 week trial license by contacting us at info@molsoft.com.
6.25.2009 Press Release San Diego, CA: Interactive Drug Design with the ICM 3D Ligand Editor
MolSoft LLC (www.molsoft.com) is a leading developer of breakthrough technologies in computational biology and chemistry. MolSoft has officially released a new ground-breaking tool for the interactive, three-dimensional (3D) design and docking of new drug candidates. The ICM Interactive 3D Ligand Editor is an easy-to-use desktop application that allows a chemist to visualize a receptor-ligand complex and then apply their experience and intuition to explore, design and optimize new drug-like compounds. Recently, this tool was validated in a community-wide evaluation of modeling and docking software where ICM performed very successfully in predicting the pose of a ligand to a G-Protein Coupled Receptor (see Michino et al Nature Reviews Drug Discovery 8: 455-456). A common scenario in drug design is that a lead compound binds reasonably well to a target protein and the ligand-receptor interactions are known, but the problem of how to improve the binding properties, synthetic feasibility, and metabolic-physicochemical properties of the ligand remains. This is where the power of the ICM 3D Ligand Editor comes in: it allows the chemist to see the ligand-receptor interactions clearly on the computer screen. Chemists can simply explore their new ideas with a click of a mouse in a fully interactive and intuitive 3D environment. The effect of a change to the ligand in terms of its interaction with the receptor is immediately displayed on the screen for the chemist's immediate evaluation. The pharmaceutical industry is already a major user of MolSoft's ICM 3D Ligand Editor technology and industry feedback has enabled MolSoft's developers to build a tool suited for chemists working in drug discovery research. Dr. Eric Martin, Director of Computational Chemistry at the Novartis Institute for Biomedical Research says "The ICM ligand editor is an extremely effective drug design tool for interactively merging the rigor of complex molecular calculations with the intuition of experienced medicinal chemists. We use it extensively both 1-on-1 at the graphics workstation, and in team meetings using a 3D projection system". So how do you use the ICM 3D Ligand Editor? The process is simple and designed to make life easier for the chemist. First, the ICM 3D Ligand Editor displays the crystal structure or model of the receptor-ligand complex along with the properties of the pocket, ligand solvent accessible surface, ligand strain or unsatisfied hydrogen bonds. The chemist can then start exploring ideas for improving the ligand by selecting a new chemical group and adding it to the ligand. The binding energy and interaction with the receptor is immediately assessed and displayed on the screen. The chemist has access to a full panel of chemical groups, linkers, bond types, stereo/isomer options and atom selections, which can be used to quickly try many different ideas. Importantly, should something be undesirable, a key feature allows the chemist to quickly undo changes to the ligand with a single mouse click and get back to the original ligand. Once the chemist has designed a ligand they are happy with, it can be saved in a single file to share with colleagues. The editor is a perfect tool for communication among scientists and can aid brain-storming session in an exciting way because hypotheses can be tested instantaneously. The ligand editor has many advanced functions that make use of MolSoft's much acclaimed ICM technology, which is the backbone of the tool. Inside the editor, features such as ligand minimization, docking, atom tethering and virtual screening are available to use. For example, thousands of chemical groups can be screened on a particular point of the ligand resulting in a ranked list of complexes. The editor can also be used for fragment based drug design and optimization. According to Professor Ruben Abagyan, MolSoft Founder and professor at the Scripps Research Institute, "This new interactive environment for lead discovery combines the best practices in flexible docking and interactive modeling. The user-friendly environment changes the way chemical probes are discovered in industry and academia. Furthermore, the freely available ICM Browser and ActiveICM plugin allow scientists to disseminate data among chemists and biologists in an interactive way." The ICM 3D Ligand Editor is part of the ICM-Chemist-Pro software product available from MolSoft LLC (www.molsoft.com).
6.4.2009 New Feature: Display Alignment Profile
A popular request from the biologists who use ICM is to develop a way to visualize sequence conservation in an alignment. Therefore in ICM version 3.6-1e (to be released soon) we have developed a way to display the sequence profile in a multiple sequence alignment. The consensus strength of a residue at a point in the alignment is visually represented by the size of the letter in the profile (see accompanying image). To display the sequence profile:
5.29.2009 MolSoft's ICM delivers star performance in GPCR modeling and docking competition.Modeling structures of G Protein Coupled Receptors (GPCRs), the most prevalent drug targets, has always been a great challenge. Predicting how and where the drugs bind to those receptors is an even greater challenge. Until recently only bovine rhodopsin and beta 2 adrenergic receptor structures have been solved. Yet, when the structure of the Adenosin receptor A2a (the receptor for caffeine) was solved in a complex with a drug, the crystallographers annouced a challenge for all modellers and dockers to predict the binding interactions of the drug with the receptor. 60 groups have registered for the competition and 29 dared to submit their models. Up to 10 models were allowed to be submitted. More importantly the models were supposed to be ranked since usually only the top predicted pose is further pursued. In a recent paper by Michino et al published in Nature Reviews the results are published (click here to read the paper). Two teams from Molsoft, Katrich-Abagyan and Lam-Abagyan built the models that had the largest number of correct ligand-receptor interatomic contacts, 45 and 34 out of 70, respecitvely out of all participants. Moreover, both models were ranked number 1, while the prediction from a competing modeler thathad better drug RMSD (when a flexible drug ring was considered) was only ranked 2. The fourth model from the Baker/Rosetta group had only 18 of correct contacts and this pose was only ranked 4th. The ICM-based GPCR modeling approach employs the Ligand-guided principle and the ICM global optimization algorithm, and its success in ligand docking shows applicability of the method to a large class of problems in the field of GPCR drug discovery.
5.15.2009 New Feature: Accent GraphicsA new edge accent feature is available in icm version 3.6-1e which will allow you to make images as shown in the pictures below. The option can be activated in the command line using: GRAPHICS.sketchAccents = yes Click on the images below:
5.10.2009 Pictures from the 2009 ICM User Group MeetingPicture by: Dr.Lars Brive (Goteborg University)
Thank you to everyone who attended the ICM User Group Meeting last month. It was a really enjoyable meeting with some great presentations. Click here to view the meeting program with speaker abstracts and bio. Thank you to Dr. Lars Brive (Goteborg University) for his photos of the lunch at the beach (small/large) and also to Prof. Bengt Persson (Linköping University & Karolinska Institute) whose photos can be viewed here:
4.16.2009 Breaking News: Scientists identify compounds using MolSoft's ICM-VLS that might fight bird flu.MolSoft's ICM-VLS was used by scientists in Canada and Hong Kong to screen the NCI ligand database to identify a synthetic compound which appears to be able to stop the replication of the influenza viruses, including bird flu virus. See the paper at J Med Chem webiste and here at MSNBC.
4.14.2009: MoSoft and Virginia Tech are awarded NIH grant to develop a new class of resistance-breaking insecticides to reduce malaria transmission.Researchers from Virginia Tech and Molsoft LLC have received a five-year, $3.557 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to continue their promising work on a new class of resistance-breaking insecticides to reduce malaria transmission. Click here for the full story.
2.1.2009 ICM-Browser-Pro Image on Front Cover of Parasitology JournalThank you to Dr. Kandeel at Gifu University in Japan who let us know that one of the images from his paper in Parasitology was included on the front cover of the January issue of Parasitology. The image was made in ICM-Browser-Pro, see the front cover here.
2008
December 2008 Newsletter MolSoft Newsletter: December 2008 In this issue:
End of Year DiscountWe 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 2009The 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:
2009 ICM User Group Meeting: Challenges in Protein Structure Prediction and Drug DesignPlease 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 ChemDownload 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 MacDue 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 VersionThe new ICM developments are listed in the Release Notes here. In particular please see:
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.
November 2008 Newsletter Welcome to the November 2008 MolSoft ICM Newsletter containing information on:
New ICM Cheminformatics Products Released
We are pleased to announce the release of two new stand alone Cheminformatics products called ICM Chemist and ICM Chemist Pro. ICM Chemist is a low cost feature-rich product for dealing with chemical structure and databases. The ICM Chemist Pro product contains all the features in ICM Chemist and gives you access to the 3D world of chemical viewing and manipuation. Some of the main features of each of the products are listed below
ICM Chemist Features
Join us at the ICM User Group Meeting in April next yearApril 9-10 2009 ICM User Group Meeting. We are looking forward to the 1st ICM User Group Meeting in April next year. The meeting schedule will include talks by experienced ICM users from around the world with an emphasis on how they have successfully used ICM and other applications for their research. MolSoft's developers and scientists will also be presenting at the meeting, so it will offer a good opportunity for you to hear about the latest ICM developments and new features. More information about how to register for the user group meeting and the speakers will be in the next newsletter.
ICM Workshop - Protein Structure and Drug Design DatesThe dates for the 2009 ICM workshops to be held in La Jolla CA are listed below.The workshops will be presented by Prof. Ruben Abagyan (Scripps Research Institute, and Founder of MolSoft ) and Dr. Maxim Totrov (Principal Scientist, Molsoft).
Feb 5-6 2009 - ICM Workshop "Protein Structure and Drug Design" October 1-2 2009 - ICM Workshop "Protein Structure and Drug Design" More details here
Google Search the ICM Manuals
The ICM Language Manual and the ICM User Guide Manual can now be google searched. Click here to give it a try. Once you have performed a search you can refine it to only display results from the Language Manual or the User Manual. This search will soon be integrated into the online versions of the manual.
See ActiveICM in Action
Click here to view an example of our new ActiveICM product (Patent Pending) in action. The files used in ActiveICM can be generated using ICM Browser Pro, ICM Chemist, or ICM Pro and ActiveICM is free to customers of this product. The online example is a Structural Genomics Consortium datapack file of PAK4 kinase. Use your left mouse button to rotate the molecule, zoom in by clicking on the left hand side of the display, scroll down the text on the left hand side and click on the blue links to see different annotated views of the protein, and right click on the graphical display for more option, and right click on the graphical display for more options.
New 3D File Format
ICM now supports the 3D XML file format which is a popular 3D format for CAD. For example, Microsoft Virtual Earth uses this file format as well as CAD software companies such as Dassault Systems. There is a big online repository of 3DXML models here, models are free to download once you have registered. Once the file is downloaded, open the ICM graphical user interface, click on File/Open in ICM to bring the file into ICM and then display the file using the ICM Workspace.
New ICM Method Publication: Atomic Property Field Chemical Superposition
The Atomic Property Field (APF) superposition method is available in ICM Chemist Pro and the details of this method have been published this year by Dr. Maxim Totrov (Molsoft, Principal Scientist). Totrov M (2008) Atomic property fields: generalized 3D pharmacophoric potential for automated ligand superposition, pharmacophore elucidation and 3D QSAR. Chem Biol Drug Des 71: 15-27
APF is a 3D pharmacophoric potential implemented on a grid. APF can be generated from one or multiple ligands and seven properties are assigned from empiric physico-chemical components (hydrogen bond donors, acceptors, Sp2 hybridization, lipophilicity, size, electropositive/negative and charge). Click here to see how to use the APF method.
Join the ICM Online Discussion Forum
We now have over 80 members in the ICM Discussion Forum but this only represents a very small percentage of the ICM users worldwide. Click here to join the forum today. It is free to join the forum and there are many benefits of being part of this group: you will always be the first to get to know the new ICM features, you will learn new tips and tricks in ICM, find out how others are applying the software in their research, and most importantly you will be part of a network of people who can support and advise you when you have an ICM question. Click here to join the forum today.
ICM Power Tip
Making Molecular Movies in ICM
To make a movie in ICM all you have to do is click on the movie button located at the bottom of the graphical user interface. Any animation or view in the ICM graphical window will then be dumped into a movie file. For more instructions please click here.
07.11.2008 July 2008 MolSoft ICM Newsletter MolSoft ICM Newsletter July 2008 Welcome to the July 2008 MolSoft ICM Newsletter containing information on:
New Features in the Latest ICM Release 3.6Fully Interactive 3D Ligand Editor
Docking a Markush Library Generate a Markush library and dock a focused version of it on the fly. See this example, optimizing the roscovitine ligand bound to CDK5 http://www.molsoft.com/gui/markush-docking.html Export Chemical Spreadsheets to Excel Export the 2D chemical sketch as well as other column data in a spreadsheet directly to Microsoft Excel. See: http://www.molsoft.com/gui/export-excel.html Read and Display Google Sketchup 3D Images
Lots of New Data Plotting Features From ICM Tables
New plotting features include:
See http://www.molsoft.com/gui/table-plot.html for instructions Background Images
IUPAC Nomenclature ICM will now determine the IUPAC nomenclature for any small molecule you sketch or read into ICM. See http://www.molsoft.com/gui/iupac.html Ribbons and Chain Breaks Display smooth ribbons and control the display of chain breaks See: http://www.molsoft.com/gui/structure-representation.html#ribbon Local Chemical Databases
Some of the features include:
For more information please click here http://www.molsoft.com/gui/local-databases.html Occlusion Shading
Protect Objects From Deletion This option is useful when making molecular documents and you do not want the viewer of the document to delete an object that is contained in the document. See: http://www.molsoft.com/gui/make-molecular-document.html#protect Wide-Screen Layout There is now a new layout for users that have a widescreen. Try it by going to File/Preferences/Gui Tab and change GUI.windowLayout New Command Line Options Other new command line options are described in the release notes .
New Product - ActiveICMActiveICM - Integrate ICM into PowerPoint or a Web Browser
Next ICM WorkshopThe next ICM workshop will be held in La Jolla CA on October 2nd to 3rd. The workshop will be presented by Prof. Ruben Abagyan (Scripps Research Institute, and Founder of MolSoft ) and Dr. Maxim Totrov (Principal Scientist, Molsoft). See http://www.molsoft.com/training.html
Events - 2008 Protein Society MeetingIf you are attending the Protein Society 22nd Annual Symposium July 19-23, 2008 in San Diego be sure to stop by the MolSoft booth and say hello. We will be holding prize draws, demonstrating all the new ICM features, and we will be available to answer any ICM questions you may have.
ICM Power TipQuick Ligand and Peptide Pocket Display
06.20.2008 MolSoft @ Bio 2008 There were over 20,000 people at the Bio 2008 meeting and we thoroughly enjoyed demonstrating the latest ICM features and answering questions from the many people who stopped by at our booth. It was great to see so many ICM-users at the meeting and meet for the first time some of our international customers from Europe, Australia, and Japan. We received great feedback on our new ligand editor feature which will be released very soon, and our patent pending molecular document technology also attracted alot of interest. Other pictures from Bio2008 can be found here.
05.22.2008 MolSoft will be Exhibiting at Bio2008 MolSoft LLC is looking forward to presenting at the Bio2008 conference in San Diego June 17-20. Please come and visit us at booth #2539 where we will be showcasing for the first time lots of exciting new tools that will be released later this year in ICM Version 3.5-2. 04.08.08 New ICM Paper: New method for the assessment of all drug-like pockets across a structural genome. Nicola G, Smith CA, Abagyan R. New method for the assessment of all drug-like pockets across a structural genome. Comput Biol. 2008 Apr; 15(3):231-40. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California. Abstract: With the increasing wealth of structural information available for human pathogens, it is now becoming possible to leverage that information to aid in rational selection of targets for inhibitor discovery. We present a methodology for assessing the drugability of all small-molecule binding pockets in a pathogen. Our approach incorporates accurate pocket identification, sequence conservation with a similar organism, sequence conservation with the host, and structure resolution. This novel method is applied to 21 structures from the malarial parasite Plasmodium falciparum. Based on our survey of the structural genome, we selected enoyl-acyl carrier protein reductase (ENR) as a promising candidate for virtual screening based inhibitor discovery.
03.20.08 New ICM Publication: A new method for ligand docking to flexible receptors New ICM publication by the Scripps Research Institute and MolSoft scientists. See: Bottegoni G, Kufareva I, Totrov M, Abagyan R. A new method for ligand docking to flexible receptors by dual alanine scanning and refinement (SCARE). J Comput Aided Mol Des. 2008 Feb 14; Paper link: Abstract Protein binding sites undergo ligand specific conformational changes upon ligand binding. However, most docking protocols rely on a fixed conformation of the receptor, or on the prior knowledge of multiple conformations representing the variation of the pocket, or on a known bounding box for the ligand. Here we described a general induced fit docking protocol that requires only one initial pocket conformation and identifies most of the correct ligand positions as the lowest score. We expanded a previously used diverse "cross-docking" benchmark to thirty ligand-protein pairs extracted from different crystal structures. The algorithm systematically scans pairs of neighbouring side chains, replaces them by alanines, and docks the ligand to each 'gapped' version of the pocket. All docked positions are scored, refined with original side chains and flexible backbone and re-scored. In the optimal version of the protocol pairs of residues were replaced by alanines and only one best scoring conformation was selected from each 'gapped' pocket for refinement. The optimal SCARE (SCan Alanines and REfine) protocol identifies a near native conformation (under 2 A RMSD) as the lowest rank for 80% of pairs if the docking bounding box is defined by the predicted pocket envelope, and for as many as 90% of the pairs if the bounding box is derived from the known answer with approximately 5 A margin as used in most previous publications. The presented fully automated algorithm takes about 2 h per pose of a single processor time, requires only one pocket structure and no prior knowledge about the binding site location. Furthermore, the results for conformationally conserved pockets do not deteriorate due to substantial increase of the pocket variability.
03.11.08 Free Online Tutorial Dates Released for May through to July. Click here for information on the upcoming online demonstrations.
03.03.08 New Review Article from MolSoft on Flexible Docking
Here is a link to a new publication in Current Opinion Structural
Biology on flexible docking by Dr. Totrov (MolSoft) and Prof. Abagyan (Scripps). The paper highlights all the recent development for including multiple receptor conformations in docking to represent ligand induced fit.
02.14.08 New Tutorial: How to model the effect of a mutation on protein structure. Click here for a new tutorial on how to make a mutation in a protein structure and optimize. 02.14.08 MolSoft Scientists Collaborate with Schering Plough to Identify New GPCR Inhibitors using ICM. Click here to read how MolSoft and Schering Plough scientists identified new inhibtitors for a GPCR using MolSoft's drug discovery products. The structure-based development of MCH-R1 and other GPCR antagonists is hampered by the lack of an available experimentally determined atomic structure. A ligand-steered homology modeling approach has been developed (where information about existing ligands is used explicitly to shape and optimize the binding site) followed by docking-based virtual screening. Top scoring compounds identified virtually were tested experimentally in an MCH-R1 competitive binding assay, and six novel chemotypes as low micromolar affinity antagonist "hits" were identified. This success rate is more than a 10-fold improvement over random high-throughput screening, which supports our ligand-steered method. Clearly, the ligand-steered homology modeling method reduces the uncertainty of structure modeling for difficult targets like GPCRs.
02.04.08 New Tutorial: How to dock to multiple receptor conformations. There is a new tutorial online here The tutorial uses Aldose Reductase as an example. Aldose Reductase has a flexible loop in the ligand binding pocket vicinity which enables a variety of inhibitors to bind and therefore in order to identify these ligands via docking it is necessary to sample the conformations of this loop and dock to an ensemble of structures.
200712.15.07 New Docking tutorials - Docking to Electron Density and Focused Markush Library Docking How to dock a ligand to an electron density map. The ICM X-Ray AutoFit is an automated method to fit a ligand into electron density. The tool combines the powerful ICM docking algorithm with an electron density fitting function. Click here for step by step instructions. How to dock a focused Markush library. A Markush library can be generated on the fly and docked using ICM. In this example we use the roscovitine ligand bound to CDK5 to identify scaffolds which may improve ligand-receptor interaction. 10.23.08 New Slide Transition EffectIn ICM version 3.5-1l a new blending transition effect between slides is available. To see this in action download the latest version of ICM or the free ICM-Browser and view this icb file: http://www.molsoft.com/~andy/blend.icb To generate this transition effect:
October 22nd 2007
As a quarter of million people fled their homes amid fierce wildfires that had burned 100,000 acres around San Diego County, Molsoft opened its doors for the families of the escapees. Children, pets, and adults have found a comfortable home at Molsoft and were given a place to stay, sleep, access internet and play video games. Games, food, laughter and partial property destruction made their stay at Molsoft more comfortable. The training class became an information center from which the families were following the fate of their homes. October 17th 2007 MolSoft launches the ICM Forum. Please sign up and contribute with questions/answers and interact with other ICM users worldwide. October 12th 2007 MolSoft announces a series of online demonstrations as a new way of teaching the ICM suite of software. Click here for more information. July 12th 2007
Molecular Movie Making Made Easy June 2nd 2007
MolCart Compound Database Update May 25th 2007 The latest version 3.5 for all ICM products has been released for Windows, Mac , Linux and SGI.Please download the latest version of ICM from our support center. Some of the new features include:
For more details please see the Release Notes.
March 27th 2007 Maxim Totrov PhD to present data at American Chemical Society National Meeting On March 27th 2007 Dr. Maxim Totrov (Principal Scientist - MolSoft LLC) will be giving a presentation entitled "Chemical superposition and pharmacophore elucidation by SCAPFOld: Self-consistent atomic property field optimization" at the American Chemical Society 233rd National Meeting & Exposition, Chicago, IL USA. The presentation abstract can be found here. March 22nd to 23rd 2007 ICM Workshop Once again the ICM Workshop sold out quickly and we had a full class of students eager to learn about Protein Structure and Drug Discovery using MolSoft's ICM software. The first day and a half of training was presented by Prof. Ruben Abagyan (Scripps Research Institute). Prof. Abagyan gave lectures and demonstrations on ICM sequence and structure analysis, molecular modeling and cheminformatics. Friday afternoon was devoted to small molecule docking, virtual ligand screening and protein-protein docking led by Dr. Maxim Totrov (Principal Scientist - MolSoft). The participants ran docking examples such as virtual screening of small ligand databases to identify known inhibitors of the cyclooxygenase receptor and protein-protein docking of subtilisin and chymotrypsin. All the participants agreed that the workshop will help them greatly when they return to the lab and would highly recommend the training to their colleagues. If you were unable to attend this workshop we are holding workshops in May and September this year. Please click here for more details and sign up early to guarantee your place. 2006 August 1st 2006 MolSoft Awarded NIH SBIR Phase I Grant to develop protein surface annotation software MolSoft was recently awarded a NIH SBIR Phase I Grant to develop an integrated protein surface annotation suite of software for biologists and chemists. The software will allow users to apply several binding site prediction methods and analyze the results. These new algorithms include a protein-protein interface prediction method for small molecule binding sites and a surface structural motif detection and visualization method. July 1st 2006 MolSoft Receives Bill and Melinda Gates Foundation AIDS Research Grant Scientists at MolSoft LLC will be working as part of a multidisciplinary team led by Susan Zolla-Pazner Ph.D. (New York University School of Medicine) on a grant funded by the Bill and Melinda Gates Foundation entitled "The V3 Loop: A Conserved Structure of gp120 that Can Induce Broadly Neutralizing Antibodies Against HIV-1" MolSoft LLC is excited to be leading the structure-based engineering of the V3-carrier immunogen. Using our experience with similar efforts we will undertake ab initio loop modeling of protein segments consisting of the central portions of the V3 signature sequences and modeling of carrier joining sequences. For more information please see the press release in the New York Times. July 1st 2006 MolSoft and Virginia Tech collaborate to work on malaria vector control MolSoft and Virginia Tech will be working together on a 3-year project funded by the Foundation of the National Institutes of Healt to apply state-of-the-art computer modeling and chemical synthetic approaches to produce highly potent and selective anticholinesterases (AChEs) for malaria vector control. MolSoft's ICM software will be used to build homology models of AChEs and virtual screening will be applied to identify selective inhibitors. ICM-Chemistry will then be applied to optimize the lead compounds. February 8th 2006: From Physics to Biology: the interface between experiment and computation BIFI 2006 - II International Conference, Zaragoza Spain. Claudio Cavasotto PhD (Senior Scientist - Molsoft) has been invited to present a talk entitled "Ligand docking and virtual screening in structure-based drug discovery" at the BIFI 2006 - II International Conference, Zaragoza, Spain. His talk will be on February 8th 2006 and more details about the conference can be found here. January 25th-27th 2006 Three-Day ICM Workshop.
January 1st 2006 MolSoft and the Mayo Clinic College of Medicine Collaboration Scientist at the Mayo Clinic and MolSoft will be collaborating on a project to model G-protein coupled receptors (GPCRs) which are key receptors for a large number of disease pathways. The aim is to use MolSoft's proprietary software to build highly-refined and rigorously validated models of GPCRs and to use these models to guide experimental work at the Mayo Clinic.
2005 September 29th-30th 2005 Successful Workshop On September 29th-30th an international group of ICM users from academia and industry gathered for our ICM Workshop entitled "Protein Structure and Drug Discovery" Click here to see what went on. August 3rd, 2005 New Version Release Molsoft has released the latest version (3.4) of ICM. This version includes a number of new features as described in the Release Notes. The most significant addition is the incorporation of ICM Molecular Documents and Presentation (Patent Pending). These can be constructed and viewed in ICM, they can consist of text linked to molecular animations and transitions. The animations and transitions are fully-interactive and can be interrupted without any loss of information. For more information on ICM Molecular Documents and Presenations please click here.
April 14th, 2005 New Product Release.
April 25th, 2005 New SGI version release.
April 5th, 2005 2004
August 10th, 2004
July 15th, 2004 July 30, 2004 California State University at Fullerton Expands Use of ICM-Pro to New Computational Biology Curriculum Being Offered in 2005-06 Molsoft is pleased to learn that the Department of Chemistry and Biochemistry at California State University, Fullerton, is expanding its teaching use of ICM-Pro. CSU Fullerton began using ICM-Pro for training undergraduate chemistry and biochemistry students in Spring 2004. ICM-Pro has also been used to teach structural bioinformatics to students seeking a Certificate in Bioinformatics through CSUFs Extended Education program. Beginning in 2005-06, ICM-Pro will be featured in a new computational biology program for chemistry and biochemistry majors [more]. July 20-21st Molsoft Conducts ICM Workshop in New Jersey USA On the 20-21st of July 2004 sixteen people attended the ICM workshop entitled "In Silico Drug Discovery". The workshop was held at Bristol Myers Squibb at Princeton New Jersey.
June 25th, 2004 Molsoft LLC is pleased to announce a collaboration with the Burnham Institute, La Jolla, on a STTR NIH funded grant entitled "15 - Deoxy -12,14-prostaglandin J2 as a ligand of RXRalpha".
March 17, 2004 Molsoft LLC Receives Phase I STTR to Develop Beta-Catenin Antagonists Molsoft LLC received a Phase I STTR award from the National Institutes of Health, National Cancer Institute, for the project entitled. Rational Development of TCF/Beta-Catenin Antagonists. The project will combine Molsoft's novel in silico lead development platform with the cancer biology resources at The Burnham Institute to discover and characterize small molecule ligands using the beta-catenin structure both alone and in complex with TCF. Beta-catenin signaling has been implicated in a number of malignancies, which makes the beta-catenin/TCF interaction an promising target for the prevention and treatment of a variety of tumors and leukemia, and the project proposes to develop a novel generation of drugs active against various forms of cancer.
2003 July 25, 2003 Molsoft LLC Receives Small Business Biodefense Grant Award Molsoft LLC received a Small Business Biodefense Program award from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, for the project entitled .Rational Design of Inhibitors of Yersinia pestis EF-Tu.. Molsoft and its research partners at the University of California, Irvine and Chemical Diversity Labs, Inc., San Diego, propose to develop a new class of antibacterial agents active against Category A pathogens likely to be used by bioterrorists including those causing plague, anthrax, cholera, and typhoid fever. Furthermore, the project proposes to develop design principles that will be useful in developing agents less susceptible to the problem of rapidly emerging antibiotic drug resistance.
18 June 2003.Mpex Pharmaceuticals and Molsoft announce collaboration for the structure-based design of new antibacterial compounds. Mpex Pharmaceuticals Inc. (“Mpex”) and Molsoft, LLC (“Molsoft’) have announced a collaboration to rationally design new antibacterial agents based on the refinement of a 3-D molecular structure of a membrane protein target, the functional characterization of its surfaces, and the application of predictive algorithms ..more..
June 16, 2003 Molsoft LLC Receives Phase II STTR Grant Award to Continue Developing Thyroid Receptor Antagonists Molsoft LLC received a Phase II STTR award from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, for continuation of the "Rational Development of Thyroid Receptor Antagonists. project. In Phase I, Molsoft and its collaborators at the NYU School of Medicine and the NYU Department of Chemistry achieved proof of concept. Molsoft.s virtual ligand screening technology was used to discover 14 small molecule thyroid receptor antagonists displaying extreme structural diversity with IC50s ranging from 4 to 30 microM. Additionally, the test-case lead optimization scheme designed in Phase I based on generating focused virtual libraries of molecules easily amenable to organic parallel synthesis resulted in the rapid identification of second generation hits with IC50 in the nanomolar range. In Phase II, Molsoft and its NYU research partners propose to conduct full-scale optimization cycles of selected hits identified in Phase 1 in order to produce low nanomolar hits and to evaluate those hits using computational tools, in vitro characterization, and preliminary animal studies. May 20th-21st 2003 Molsoft LLCConducts Annual Spring Training CourseOn the 20-21st May 2003 conducted an ICM workshop entitled "In Silico Drug Discovery". The workshop was held at Molsoft LLC La Jolla.
2002 21 October 2002. Molsoft to Evaluate Novel Scaffolds for PDF Inhibitor Program Molsoft LLC, a La Jolla based company providing new, breakthrough technologies in computational chemistry and biology, and GeneSoft Pharmaceuticals Inc., a specialty pharmaceutical company headquartered in South San Francisco, announced that they have signed a collaborative agreement to evaluate inhibitors of peptide deformylase (PDF), an essential bacterial metalloenzyme and novel antibiotic target ..more... 26 August 2002. Molsoft Conducts Training Course/ Workshop in La Jolla, CA Molsoft conducted an intensive 2-day training course/workshop on the ICM suite of products at La Jolla, CA. The lecture and hands-on demonstrations covered topics of interest to computational chemists and biologists in the area of drug discovery. The topics included molecular graphics, animation, bioinformatics, homology, protein modeling, docking and ICM command language for expert users. The attendance was international with scientists coming from Asia and Europe as well as from various parts of the US. The attendees were interested in having future courses, both at the basic and at the advanced levels. One of the attendees from Australia who is very well known in the modeling field for his early work in structural bioinformatics, Dr. Jiri Novotny (Consultant for Biocomputing and Bioinformatics), said, "The course was well organized and presented the participants with two full days of new and efficient tools applicable to the most pressing problems of current structural biology and bioinformatics: structural/functional annotation of genomic data, analysis of protein surfaces, ligand binding sites, virtual ligand screening, structure derivation, regularization and model building". He continued on to say, "Perhaps the most impressive aspect of the workshop was the skill, dedication and the highest professional standard of the scientific team established at Molsoft by Prof. Abagyan. In hands-on session at computer screens the participants were encouraged to ask questions and bring out problems that were answered and solved immediately by the whole team including themselves. It was an invaluable practice and a good demonstration of the speed and versatility of the newest ICM version."
About the training course, Dr. Maxim Totrov, co-founder and Principal Scientist at Molsoft said, "The course provided us with a vital opportunity to meet members of the growing community of ICM-users and bring them up-to date with the latest developments in ICM. It was exciting to see first-time users perform complex molecular modeling tasks such as protein-ligand docking after only a few hours of training. These workshops are geared towards helping our customers utilize fully the power of ICM molecular modeling suite in their everyday work." 22 August 2002. Molsoft Participates in the Annual Symposium of the Protein Society in San Diego
"We enjoyed talking to numerous visitors to our booth," said Dr. Lalitha Subramanian, Director of Contract Research for Molsoft, "many of whom were extremely excited to see ICM's new GUI interface." She added, "Our science has always been strong and well validated. Now, with the added power of a very user friendly interface, ICM will be the choice for most researchers in the academic and commercial fields." Molsoft also participated in the Beyond Genome 2002 conference held in June of this year and will be presenting at the BioITWorld conference to be held in November. Molsoft LLC Receives Phase II SBIR Grant Award May 21, 2002 Molsoft received a Phase II SBIR award from the Department of Energy for continuation of the "GAP: Genomics Annotation Platform" project. In Phase I Molsoft used its many years of experience in developing molecular visualization and manipulation software to built the computational tools central to the functionality of the GAP. In Phase I, Molsoft successfully used GAP to predict the function of uncharacterized genes. In Phase II, Molsoft will optimize the existing tools and develop an efficient graphical user interface while adding a system for automatic updates to GAP. When completed, the Molsoft GAP will provide an online research platform allowing users from the pharmaceutical industry to access Molsoft's state-of-the-art computational biology technology and to use that technology for extracting meaningful information from the human genome project and from other major, international sequencing efforts. March 2002 Molsoft received a Phase 1 SBIR grant from the National Institutes of Health, National Human Genome Research Institute for its project entitled "Sequence/Structure Annotation of Protein Families." The goal in this project is analyzing in silico well known protein families in order to identify which family members could be good therapeutic targets and how pharmacogenomics strategies can be devised to better design drugs targets at these proteins.
2001 August 2001 Molsoft and Plexus Vaccine Inc.entered into a licensing agreement to discover and commercialize new interventional strategies for global infectious diseases, for drug-resistant microbes, and for chronic diseases associated with cryptic pathogens. Plexus will use the Molsoft ICM software suite to develop Virtual Epitope databases of molecular disease targets for in silico design of structural mimics that can be readily synthesized, tested, and formulated as vaccines ..more.. August 2001 Molsoft received a Phase 1 SBIR grant from the Department of Energy for its project entitled "GAP: Genomics Annotation Platform." The goal in this project is to develop bioinformatics tools used for predicting the function of uncharacterized genes. May 2001 Molsoft and HTS Biosystems, Inc. (HTS) entered into collaboration for Molsoft to develop software modules for instrument control, data collection, local visualization, and analysis of data generated by HTS' Surface Plasmon Resonance (SPR) instruments. April 2001 Molsoft LLC and Chemical Diversity Labs, Inc. (CDL), San Diego, CA, formed a strategic alliance to provide joint chemistry and computational modeling services to their customers. Molsoft will use known three-dimensional structures of drug targets as the starting point for the rational selection process. The Molsoft modeling by homology technology will be applied in cases when the structure is not available. CDL will give Molsoft an access to its collection of over 250,000 diverse purified small molecules already available for biological screening. February 2001 Molsoft and Biovitrum AB, a subsidiary of Pharmacia & Upjohn AB, entered into an agreement to co-develop a Chem-Informatics Client System. Molsoft and Biovitrum will use Molsoft's proprietary programming languages and libraries to develop the software, which will be called BeeHive and will function as a program manager and database interface for chemical searches, analysis, and integration.
2000 November 2000 Molsoft has moved to a new location, click the press release for more details. October 2000 Molsoft and Syrrx, Inc., a pioneer in the field of structural proteomics, entered into a strategic alliance to accelerate structure-guided drug discovery through the combination of Molsoft's Virtual Ligand Screening (VLS) technology and other computational biology technologies with Syrrx's high-throughput structural proteomics platform. ..more.. September 2000 Molsoft received a Phase 1 STTR grant from National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases for its project entitled "Rational Development of Thyroid Receptor Antagonists." The goal of this project is to discover and optimize small molecule antagonists of the thyroid hormone receptor. Molsoft will work with the New York University School of Medicine to complete the project. September 2000 Molsoft LLC announced the relocation of its headquarters and commercial development operations to an expanded facility in La Jolla. The new facility will accommodate several expanded programs, including the continued refinement of ICM 2.8, the expansion of software sales and the addition of new products and in-house services. The new facilities include 3500 square feet of computer laboratory, research, training, and office space in close proximity to The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF), both of whom have research collaboration agreements with Molsoft. September 2000 Molsoft LLC announced its first shipment of the Molsoft BioPackage to Hitachi, Ltd. for distribution in Japan. During the two-year Distribution Agreement, which became effective June 1, 2000, Hitachi will be the exclusive distributor of Molsoft's BioPackage in Japan. Hitachi plans to market the software to Japanese corporations, universities, and laboratories. Molsoft's computer software provides novel computational and informational technologies for biomedicine including genomics and drug discovery. ..more.. April 2000 Molsoft and The Genomics Institute of the Novartis Research Foundation (GNF) have entered into a Research Collaboration Agreement. The collaboration will focus on the further development of computational biology tools for functional and structural annotation of new genomic sequences, protein modeling, and virtual ligand screening. Molsoft will provide its ICM software for research in functional and structural annotation of new genomic sequences, protein modeling and lead discovery at GNF, which will provide GNF researchers with an accurate, speedy and flexible method for structural annotation and protein structure modeling. Molsoft will grant GNF a nonexclusive license to use Molsoft databases and software in gene discovery, functional genomics, and drug discovery, and GNF will supply support for personnel and computer facilities to be used in the joint tool development projects ..more.. July 2000 Molsoft LLC and The Scripps Research Institute (TSRI), a private, non-profit research organization engaged in basic biomedical research, announced the formation of research collaboration. During the term of the agreement, TSRI and Molsoft will collaborate on defined joint projects involving the functional and structural annotation of new genomic sequences and protein modeling. For the joint projects, Molsoft will grant TSRI a nonexclusive and restricted license to use Molsoft databases and software in gene discovery, functional genomics and drug discovery, and TSRI will supply personnel and computer facilities for use in the joint projects. ..more..
1999 November 1999 Molsoft LLC and eBioinformatics, Inc. announced the formation of an alliance in which Molsoft will provide its ICM software for incorporation into eBioinformatics, Inc. flagship product BioNavigator. The Molsoft-ICM suite of computational biology tools will provide BioNavigator users with access to the latest and most powerful algorithms. This alliance will give scientists new opportunities based on the power of Molsoft's ICM software and the convenience of BioNavigator's web-based bioinformatics workspace ..more..
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You can now read, render and display any 3D object in ICM. e.g. KMZ and COLLADA format directly from the google sketchup website. We have also added options for changing the texture and material of a 3D object. See 
On January 25th-27th 2006, a 3-day ICM Workshop was held at Molsoft's La Jolla
offices. The first two days of the workshop covered all aspects of protein
structure and drug discovery including sequence analysis, protein modeling,
small molecule docking, protein-protein docking, cheminformatics and QSAR. The
third day was dedicated to advanced ICM training including the ICM command
language, scripting, loop modeling and flexible receptor docking. The course was conducted by Prof. Ruben Abagyan (The Scripps Research Institute) and
Dr. Maxim Totrov (Principal Scientist - Molsoft).
The new version, ICM 3.0, was introduced at the course and was well accepted as
an extremely user-friendly interface by the attendees. This version, which also
has stereo viewing mode that works with VRex glasses on Linux and Windows
platforms, was welcomed by all the participants as an efficient and low cost
alternative to existing stereo viewing tools.
Molsoft is pleased to announce its participation at the Protein Society's 16th
Annual Symposium held at the Marriott in San Diego from August 17-21, 2002.
Attendance was estimated at around 1300. Molsoft's exhibit was designed to
inform Protein Society attendees about the latest technology available from
Molsoft including its recent version of a new graphical interface which enables
Molsoft's ICM software easier to use than ever before.
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