SMARTCyp has been updated to version 2.1.1. SMARTCyp is a method for prediction of which sites in a molecule that are most liable to metabolism by Cytochrome P450 a major contributor to oxidative metabolism.

The latest update now includes models for prediction of CYP2D6 and CYP2C9 specific metabolism

I’ve just completed a review of CheS-Mapper.

CheS-Mapper (Chemical Space Mapper) is a 3D-viewer for chemical datasets of small molecules, a recent publication in the Journal of Chemiformatics describes the application DOI: 10.1186/1758-2946-4-7, In addition more information is available on the wiki page. Whilst there are many applications for the visual analysis of data, very few provide the tools needed to handle chemical structures, CheS-Mapper is a java application that runs under Mac OSX (I only tested Lion) based on the Java libraries Jmol, CDK, WEKA, and utilizes OpenBabel and R, that provides an interesting means to explore chemical data sets.

There a complete list of software reviews here.

Chemkit is an open-source C++ library for molecular modelling, cheminformatics, and molecular visualization.

Sdfchecker is a free inspection and manipulation program for SDFiles (.sdf). Summary of functions: - Indicate number of structure records - Indicate number of blank structure records - Display list of Data Field names - Remove blank structure records - Split large files into smaller multiple files, a single random sized file, or containing a specified range of records - Convert into individual MOL files - Inspect for duplicate Data Field names within each record

The Mobile Molecular DataSheet (MMDS) has been updated. Two major usability enhancements:

(1) Additional tool banks on the left and right side of the sketcher provide simplified drawing tools that are more familiar to users of desktop chemical drawing software.

(2) A tooltip system provides tips, live demonstrations and links to documentation.

I recently wrote a couple of Applescripts that use the Chemical Identifier Resolver (CIR) a web service that performs various chemical name to structure conversions and it occurred to me that is should be possible to use this service to generate images for use as popups on a graph in the same way that I’ve previously described using Flot and ChemSpider. This works well but relies on the structure already being in the ChemSpider database, for novel structures we need a service for generating the image from a chemical identifier. CIR provides a simple web service for doing exactly this, for example submit a SMILES string and it can return a 2D image.

This tutorial shows how to create an interactive plot using Flot and CIR

From the KNIME newsletter

“…good news for our Mac Users! We have just released KNIME 2.5.4 which fixes issues caused by the latest Apple update of the Java environment. We are grateful to the very active KNIME community which has helped to identify and fix this problem.”

KNIME Desktop 2.5.4 can be downloaded from the download page (http://www.knime.org/download) or you can upgrade your existing KNIME installation by using the built-in update functionality available in the "File" menu

There is also a KNIME tutorial here

Biscu-it™ is a collection of - hopefully - useful Python tools and functions that have been built on top of the RDKit chemoinformatics toolkit and that have been wrapped in a single Python package called Biscu-it™.

Virtual models for property Evaluation of chemicals within a Global Architecture (VEGA), Using the VEGA platform, you can access a series of QSAR (quantitative structure-activity relationship) models for regulatory purposes, or develop your own model for research purposes. QSAR models can be used to predict the property of a chemical compound, using information obtained from its structure. This version comes with some minor error fixes and with a new model (BCF Read-Across).

There is an interesting publication in Journal of Cheminformatics 2012, 4:7 doi:10.1186/1758-2946-4-7 describing CheS-Mapper .

CheS-Mapper (Chemical Space Mapper) is a 3D-viewer for chemical datasets with small compounds.
It can be used to analyze the relationship between the structure of chemical compounds, their physicochemical properties, and biological or toxic effects. CheS-Mapper divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity.

I’ve been doing a little work to update iBabel, I’ve updated all the tools developed by Silicos-it to use the new names and options.

The SVG support in Openbabel has undergone significant improvements due to the brilliant efforts of Noel O’Boyle and Chris Morley in particular the ability to colour a substructure within a molecule. This requires installation of the development version of OpenBabel at present.

I’ve added a movie to show it in action.

I’ve just posted a review of Stardrop an application from Optibrium that is designed to aid decision making for scientists involved in drug discovery.

One of the critical activities of most drug discovery programs is the identification of novel leads, these hits can come from high throughput screening or fragment-based screening There is however great interest in virtual screening which allows the evaluation in silico of a vast number of compounds and the selection of a subset that have a greater chance of desired activity. The virtual screening can be achieved by searching using sub-structures or molecular descriptors, by docking potential ligands into the target protein and scoring the resulting docked pose, or by comparing with the shape and/or electrostatic map of a known ligand.

Shape-it is a tool developed by Silicos-it that aligns a reference molecule against a set of database molecules using the shape of the molecules as the align criterion. It is based on the use of Gaussian volumes as descriptor for molecular shape as it was introduced by Grant, J.A.; Gallardo, M.A.; Pickup, B.T. (1996) ‘A fast method of molecular shape comparison: a simple application of a Gaussian description of molecular shape’,J. Comp. Chem. 17, 1653-1666.

This script shows how to run shape-it from within Vortex, bringing in the shape matching scores for filtering and analysis.

MolSoft have announced the release of ICM version 3.7-2c.

New features include Atomic Property Fields 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).

The 3D ligand Editor is a powerful new tool for the interactive design of new lead compounds in 3D. It allows you to make modifications to the ligand and see the affect of the modification on the ligand binding energy and interaction with the receptor.

Use AQUASITES to design chemicals based on their ability to displace or keep water molecules inside the ligand binding site of proteins. The first step is to identify water binding sites and then the second step is to estimate the free energy of water displacement for a particular ligand(s).

Protein Modelling Inside ICM there are many features for homology modelling and loop modelling. This new option can be used if you have a gap in your protein and you want to find loops in the PDB which fit the gap.

"Pipe-able" Scripting in ICM. New options to pipe icm commands and scripts. Easy way to write pipe-able scripts (see $ICMHOME/molpipe/*.icm). Easy way to add parallelism to unix/mac ICM scripts: fork with pipe option ($ICMHOME\molpipe*.icm)

I’ve just added a new Vortex script, this one uses a PERL script that is part of the excellent MayaChemTools.

Scripting Vortex Using OpenBabel
Scripting Vortex 2 Using filter-it
Scripting Votrex 3 Using cxcalc
Scripting Vortex 4 Using MOE
Scripting Vortex 5 Calculating similarities using OpenBabel
Scripting Vortex 6 Filtering compounds
Scripting Vortex 7 Using MayaChemTools

I’ve just added another Vortex script. In this script we will make use of the ability of filter-it to categorise input molecules into 1) a set of molecules that fulfil all criteria as defined in the filter definition file (passed molecules), and 2) a set of molecules that do not fulfil at least one of the defined filter criteria (failed molecules). The filter file defines the criteria for acceptable calculated phisicochemical properties and also any substructures that should be included or excluded during the filtering. The filter file is a simple text file that users can define for themselves, there is a detailed explanation on the silicos-it website. They also provide several example filters “Leadlike”, “Druglike”, “CMCLike” and “Clean” which cleans up a file without imposing a “drug like” filter. It should be relatively straight-forward for users to create their own filters, one could imagine a rule-of-3 filter that might be used in fragment-based screening approaches, or a toxicphore filter based on SMARTS shown to be implicated in a specific toxicity. It might also be possible to define project specific filters if a project requires a specific profile. If you need help it might be worth contacting Silicos-it.

I’ve mentioned Silicos-it in the past and I thought I’d highlight them again since they have had a major makeover, the website has moved and the tools have been updated and renamed.

Silicos-it has contributed it’s expertise to the chemoinformatics community by porting its source code into the open source domain. Examples include the spectrophore descriptors, the filtering program filter-it and the pharmacophore tool align-it.

Command-line tools

Filter-it™ is a command-line program for filtering molecules with unwanted properties out of a set of molecules. The program comes with a number of pre-programmed molecular properties that can be used for filtering.

I used the filter-it (previously called Sieve) in a Vortex script, I’ve rewritten the script and the tutorial to account for the name change.

Strip-it™ is a tool to extract molecular scaffolds according predefined rules. These rules are based on the definitions of scaffolds as described by Bemis & Murcko (J. Med. Chem. 1996, 39, 2887), Pollock (J. Chem. Inf. Model. 2008, 48, 1304) and Schuffenhauer (J. Chem. Inf. Model. 2007, 47, 47).

Align-it™ is a pharmacophore-based tool to align small molecules. The tool is based on the concept of modeling pharmacophoric features by Gaussian 3D volumes instead of the more common point or sphere representations. The smooth nature of these continuous functions has a beneficent effect on the optimisation problem introduced during alignment.

Shape-it™ is a shape-based alignment tool by representing molecules as a set of atomic Gaussians. The software is based on the method described by Grant and Pickup (J. Phys. Chem. 1995, 99, 3503).

Spectrophores are one-dimensional descriptors generated from the property fields surrounding the molecules. This technology allows the accurate description of molecules in terms of their surface properties or fields. Comparison of molecules’ property fields provides a robust structure-independent method of aligning actives from different chemical classes. When applied to molecules such as ligands and drugs, Spectrophores can be used as powerful molecular descriptors in the fields of chemoinformatics, virtual screening, and QSAR modeling. The Spectrophore code was developed by Silicos, and donated to the OpenBabel project in July 2010.

I’ve added two new applications from Metamolecular to the alphabetical listing.

ChemVector™ offers a modern solution to the chemical structure imaging problem. Features

• 100% JavaScript. No browser plugins are necessary.
• Runs with all commonly-used browsers on Windows, Linux, Mac, and iPad. This includes Internet Explorer 6-9 in addition to Firefox, Google Chrome, and Safari.
• Renders structures directly from individual molfiles on a server, or as inline content.
• Renders chemical structure content directly from ChemDraw™ binary files (.cdx).
• Declarative syntax replaces <img> tags with analogous <object> tags, making it easy for both developers and designers to work with the resulting markup.
• Non-blocking implementation makes it possible to render dozens of structures on a single page while maintaining UI responsiveness.
• Structures can be magnified pre- or post-rendering with no pixelation.

ChemCore is the chemiformatics foundation of all of the Metamolecular products and services. Written in Java and cross-compilable to a number of target runtimes and platforms, ChemCore is both fast and flexible.

Features

• Fast subgraph matching
• Powerful graph query capabilities
• Flexible, efficient graph traversals
• Fast file input/output
• A complete system of atomic weights and elemental properties
• Sensible handling of implicit hydrogens
• Molecule validation and correctness-checking
• Molecule transformations, including canonicalization and salt-stripping
• 100% Java cross-compilable to JavaScript and other target runtimes and platforms
• Extensively tested and documented

I was reading the announcements of new products from OpenEye and I thought I should update the listings.

AFITT from OpenEye is the only software to offer a fully automatic ligand fitting process that optimizes a real-space fit to density while keeping conformational strain to a minimum. It capitalizes on a combination of core technologies that OpenEye has developed, specifically conformer generation, shape potential, high quality small molecule structure minimization, and visualization. The key step, after finding the appropriate conformers and aligning them to density, is the implementation of a refinement that combines force field and shape potentials, via a series of adiabatic optimizations [1]. The AFITT distribution includes both a GUI and a collection of command-line applications.

BROOD is a software application designed to help project teams in drug discovery explore chemical and property space around their hit or lead molecule. BROOD generates analogs of the lead by replacing selected fragments in the molecule with fragments that have similar shape and electrostatics, yet with selectively modified molecular properties. BROOD fragment searching has multiple applications, including lead-hopping, side-chain enumeration, patent breaking, fragment merging, property manipulation, and patent protection by SAR expansion.

FILTER is a very fast molecular filtering and selection application. It uses a combination of physical property calculations and functional group knowledge to remove undesirable compounds before they enter experimental or virtual screening. Undesirable properties may include: toxic functionalities, a high likelihood of binding covalently with the target protein, interfering with the experimental assay, and/or a low probability of oral bioavailability.

QUACPAC provides pKa and tautomer enumeration in order to get correct protonation states. It also offers multiple partial charge models (including MMFF94 [1], AM1-BCC [2], and AMBER [3]) that cover a range of speed and quality in order to allow appropriate charging for every end use. QUACPAC's approach to tautomeric enumeration is to provide multiple tautomeric states rather than one "correct" tautomer. Subsequent downstream processes are then used to identify the appropriate tautomeric form.

SZYBKI optimizes molecular structures with the Merck Molecular Force Field, either with or without solvent effect, to yield quality 3D molecular structures for use as input to other programs. Since the chemistry of molecular interactions is a matter of shape and electrostatics, it is impossible to consider either without reasonable 3D molecular structures. SZYBKI also refines portions of a protein structure and optimize ligands within a protein active site, making it useful in conjunction with docking programs.

I’ve just posted the latest tutorial on scripting the chemically intelligent spreadsheet application Vortex, this tutorial shows how to use OpenBabel to provide similarity searching.

The full list of Vortex scripting tutorials are shown below.

Scripting Vortex Using OpenBabel
Scripting Vortex 2 Using Sieve
Scripting Votrex 3 Using cxcalc
Scripting Vortex 4 Using MOE
Scripting Vortex 5 Calculating similarities using OpenBabel

More hints and tutorials can be found here.

This might be of interest.

Dotmatics is looking to expand the team working on Vortex, its data analysis platform. The candidate should have several years software development experience with Java and preferably with the Swing graphical user interface toolkit. The ideal candidate will have a degree or PhD in the life sciences, and will have experience with data visualisation and analysis techniques such as clustering. Experience with cheminformatics systems or statistical software, such as R, will be advantageous. Candidates will probably have experience working within the pharmaceutical/biotech sector or the life science software development industry.

The position will be based at the UK headquarters in Bishops Stortford (Herts, UK). We offer a competitive salary, benefits and a pleasant working environment at the Old Monastery site. Further information about the company and our software can be found at http://www.dotmatics.com.

This is the fourth tutorial on scripting Vortex a chemically intelligent data visualisation package. In the previous tutorials we have looked at getting data from OpenBabel, sieve, and cxcalc in this tutorial we will be using MOE as the compute engine. MOE from Chemical Computing Group is probably best known as a graphical user interface to a suite of computational chemistry tools, whilst this is indubitably the means by which many users will interact with the program it is worth finding out about the command-line tools that are available. These tools are often accessed by pipeline tools such as Knime to allow rapid processing of large files. CCG provides four very useful command-line tools in particular sddesc allows the calculation of some or all of the MOE molecular descriptors for each molecular entry.

The Vortex Scripts

Scripting Vortex Using OpenBabel
Scripting Vortex 2 Using Sieve
Scripting Votrex 3 Using cxcalc
Scripting Vortex 4 Using MOE

Whilst Vortex has tools that allow you to do some analysis and of course you can use the scripting facility to access statistical or model building packages like R in this tutorial we will be using a model taken from the literature and implementing it within Vortex using a calculation field to construct the algorithm.

KNIME (Konstanz Information Miner) is a user-friendly and comprehensive open-source data integration, processing, analysis, and exploration platform. From day one, KNIME has been developed using rigorous software engineering practices and is used by professionals in both industry and academia in over 60 countries.

Release Date: December 1, 2012 Enhancements

• Enh 2933: Database Schema Browser for Database (Connection) Reader nodes
• Enh 2924: Database (Connection) Reader allows executing multi-line SELECT and non-SELECT queries
• Enh 2976: New Database dialog "Connection" tab more user friendly UI
• Enh 2952: Node-Annotations (multiline labels) replacing one-line labels underneath a node
• Enh 2882: Sort data in table view by clicking the column header
• Enh 2914: TableView supports Ctrl-C on a single cell
• Enh 2959: Tips & Tricks dialog is shown when KNIME starts
• Enh 2934: New editor action that allows to align nodes vertically (in addition to align horizontally)
• Enh 2928: Automatic checks for updates during startup (added command line argument "-checkForUpdates")
• Enh 2840: Missing Value node multiple column selection in Individual tab
• Enh 2876: Resolved Rename node name confusion: new name: Column Rename
• Enh 2975: Decision Tree View has zoom functionality
• Enh 2980: Weblog Reader is now able to read compressed files
• Enh 2974: File browsers in reader nodes (SDF, CSV, etc.) open with directory of currently selected file
• Enh 2907: XPath node can return missing value instead of empty string/NaN for non-matches
• Enh 2908: XPath node allows returning of attributes in a node set (multi-matches)
• Enh 2937: SubsetMatcher node allows mismatches
• Enh 2878: Add hidden debug option to initialize sorter memory service
• Enh 2883: Added ability to parallelize computation in ColumnRearranger
• Enh 2958: Added #clearHistory method for FileChooserHistory
• Enh 2964: Color chooser DialogComponent and SettingsModel is added
• Enh 2271: Upgrade of CDK integration (better renderer, SMARTS parsing) - part of community extensions

There is a KNIME Tutorial here

ChemAxon's Calculator (cxcalc) is a really useful command line program in Marvin Beans and JChem that performs chemical calculations using calculator plugins. There are a lot of calculations provided by ChemAxon (e.g. charge, pKa, logP, logD), and others can be added by writing custom plugins, perhaps one of the most useful is the ability to calculate the acidic and basic pKa. Calculation of pKa is essential to get a reasonable hold on the LogD of a molecule. LogD is probably the most critical physicochemical property in drug discovery, it has a major influence on absorption, cell penetration, metabolism, CYP450 inhibition and induction, PGP transporter activity and activity at the HERG channel, and is often a critical component of any structure activity relationship.

These scripts make use of cxcalc to generate data columns in Vortex

This is the second page on scripting Vortex, on the first page I described how to use OpenBabel to calculate a limited selection of chemical properties. In this script we will use one of the brilliant tools from silicos.

SIEVE is a program for filtering out molecules with unwanted properties. It is based on the Open Babel open source C++ API for rapid calculation of 45 different molecular properties.

• Jamberoo (former JMolEditor) a java program for displaying, analyzing, editing, converting, and animating molecular systems.

• Fconv is a command-line tool for several tasks concerning manipulating, converting, and analyzing data from different file formats

A selection of extensions that should be useful for chemists.

Chemspider :- Displays structure of highlighted chemical/drug and links to ChemSpider page.
PubChem :- Search PubChem for the highlighted compound
eMolecules :- Search eMolecules for the highlighted compound
Chemicalize :- Submit the current URL to chemicalize.org
DrugBank :- Search DrugBank for the highlighted compound

• Indigo is an organic chemistry toolkit. The code base is shared among the projects. All of the tools are written in C++, while a number of C# and Java wrappers are available.

• Highly experimental version of KNIME 2.1 released for Mac OS X.

Molegro Data Modeller is a cheminformatics application for Data Mining, Data Modelling, and Data Visualization.

• Instant JChem Personal (an new OS independent desktop application for working with chemical and non chemical data) and Marvin, a chemical editor and viewer suite are free for all users
• All products are free for academic teachers and researchers - including the enterprise edition of Instant JChem
• Most products are free for freely accessible, non commercial websites