Depth-First: Tag structure

ChemWriter, Chemical Structures, and the Web

Rich Apodaca — Tue, 27 Nov 2007 12:09:00 +0000

Of all the components that make up today's cheminformatics systems, the 2D structure editor may be the most widely-used. A 2D structure editor is often a chemist's first and most enduring exposure to cheminformatics, and can be encountered as early as Junior High or High School.

Over time, a good 2D structure editor becomes every bit as important to a chemist as a text editor is to a writer or software developer. At any given ACS organic division symposium, you're likely to find several bench chemists who only casually, if ever, use a 3D molecular modelling program; finding any who don't regularly use a 2D structure editor would be much more challenging.

2D structure editors are ubiquitous. They can be found in one form or another in most cheminformatics systems, ranging from databases, to standalone applications, to property calculators, and even 3D molecular modelling programs.

Despite the importance of structure editors, they don't get much attention among cheminformatics developers. For example, if your bibliography is anything like mine, it contains dozens of papers on molecular descriptors. Yet the number of cheminformatics papers describing the design of ergonomic chemical structure editors is, well, one or maybe two.

About ChemWriter

ChemWriter™ is a new product aimed at making 2D chemical structure editors a lot more interesting, easy to use, and versatile than they have been in the past. Designed specifically as a lightweight, extendable component, ChemWriter is ideal for use in chemically-enabled Web applications.

The second beta version of ChemWriter has recently been released by my company, Metamolecular, LLC. A recent article on the Metamolecular company blog discusses ChemWriter in more detail.

The Structure Editor In-Depth

Because the design and use of 2D chemical structure editors is an unusual subject in cheminformatics, a compilation of articles on the topic from Depth-First and the Metamolecular Web site is provided below. Many of these articles refer to "Firefly", which was ChemWriter's name during early development.

Why the Structure Editor Matters

The Structure Editor: (Forgotten) Link Between Chemistry and Cheminformatics Title says it all.
Four Free 2-D Structure Editors for Web Applications An early look with example code.
Waldorf Salad Why aesthetics matter in chemistry.

Creating ChemWriter

A 2D Chemical Structure Editor for the Web: Embracing Constraints in Firefly Creating remarkable products depends on identifying and embracing constraints.
A Chemical Structure Editor for the Web: Four Screenshots of a Firefly Prototype Some screenshots of an early ChemWriter prototype.
A Chemical Structure Editor for the Web: Firefly's Two Audiences A good structure editor needs to delight both developers and end users.

Using ChemWriter

Open Notebook Science Using InChIMatic ChemWriter in action.
Googling for Molecules with InChIMatic and Firefly One application of InChI using ChemWriter.
Top Ten Best-Selling Drugs Worldwide (2006) - Depth-First Structures courtesy of an early development version of ChemWriter Desktop.
Top Ten Best-Selling Drugs Worldwide With Structures 2006 - Metamolecular ChemWriter can also be used to dynamically render resizable 2D chemical structures in Web pages.
ChemWriter and the Java Deployment Toolkit A simplified method for cross-browser applet deployment using ChemWriter.
Transferring Molecules With ChemWriter Demonstrates how JavaScript can be used to move molecular information into and out of ChemWriter.

Extending ChemWriter

Building a Molecule Preview with Firefly: The Joy of Swing Shows one use for ChemWriter as a Swing GUI component.
Making Your 2D Structures Look Good: Firefly, Styles and Stylesheets Every aspect of ChemWriter's rendering can be customized, as is shown with this early development version of ChemWriter Desktop.
Never Draw the Same Molecule Twice: Viewing Image Metadata Embedding 2D structure information as a molfile in PNG images.
Editable and Searchable 2D Molecular Images Metadata applied in a novel way using a development version of ChemWriter Desktop.

From IUPAC Nomenclature to 2-D Structures With OPSIN

Rich Apodaca — Tue, 17 Oct 2006 13:57:00 +0000

A previous article introduced OPSIN, an Open Source Java library for decoding IUPAC chemical nomenclature. In this tutorial, you'll see how OPSIN can, when interfaced with freely-available chemical informatics software, generate 2-D structure diagrams from IUPAC names.

Prerequisites

This tutorial requires Ruby CDK (RCDK), which in turn requires Ruby, Java, and the Ruby Java Bridge. Tutorials detailing the installation of RCDK on both Windows and Linux platforms are available.

In addition, you'll need a copy of the standalone jarfile opsin-big-0.1.0.jar. Future versions of RCDK will integrate the OPSIN jarfile, making this step unnecessary.

Outlining the Problem and a Solution

We'd like to create a simple Ruby class with a method that accepts an IUPAC chemical name as input and produces a PNG image of the corresponding molecule as output. OPSIN accepts IUPAC names as input, but it only produces Chemical Markup Language (CML) as output. The CML output lacks 2-D coordinates, and OPSIN itself has no 2-D rendering capabilities.

We'll use RCDK to augment OPSIN's capabilities. Thanks to CDK's built-in CML support, RCDK can read CML and generate an AtomContainer representation. RCDK also supports the assignment of 2-D coordinates to an AtomContainer via CDK's StructureDiagramGenerator. To produce the PNG image, we'll use the 2-D rendering capability made possible through Structure-CDK, which is a built-in component of RCDK.

A Simple Ruby Library

Create a working directory and copy opsin-big-0.1.0.jar into it. Next, create a file called depictor.rb containing the following Ruby code:

require 'rubygems'
require_gem 'rcdk'
require 'rcdk'

Java::Classpath.add('opsin-big-0.1.0.jar')

require 'util'

# A simple IUPAC->2-D structure convertor.
class Depictor
  @@StringReader = import 'java.io.StringReader'
  @@NameToStructure = import 'uk.ac.cam.ch.wwmm.opsin.NameToStructure'
  @@CMLReader = import 'org.openscience.cdk.io.CMLReader'
  @@ChemFile = import 'org.openscience.cdk.ChemFile'

  def initialize
    @nts = @@NameToStructure.new
    @cml_reader = @@CMLReader.new
  end

  # Writes a <tt>width</tt> by <tt>height</tt> PNG to
  # <tt>filename</tt> for the molecule described by
  # <tt>iupac_name</tt>.
  def depict_png(iupac_name, filename, width, height)
    cml = @nts.parseToCML(iupac_name)

    throw("Can't parse name: #{iupac_name}") unless cml

    molfile = cml_to_molfile(cml)

    RCDK::Util::Image.molfile_to_png(molfile, filename, width, height)
  end

  private

  def cml_to_molfile(cml)
    string_reader = StringReader.new(cml.toXML)

    @cml_reader.setReader(string_reader)

    chem_file = @cml_reader.read(@@ChemFile.new)
    molecule = chem_file.getChemSequence(0).getChemModel(0).getSetOfMolecules.getMolecule(0)

    molecule = RCDK::Util::XY.coordinate_molecule(molecule)

    RCDK::Util::Lang.get_molfile(molecule)
  end
end

Testing, Testing

A short test will demonstrate the capabilities of the Depictor library. Add the following to a file called test.rb in your working directory (or enter it interactively with irb):

require 'depictor'

depictor = Depictor.new
name = '3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid' #Penicillin G

depictor.depict_png(name, 'out.png', 300, 300)

Running this test produces a 300x300 PNG image of Penicillin G, named out.png, in your working directory:

As you can see, this simple library and test code has:

correctly parsed the rather complex IUPAC name (3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2- carboxylic acid) to a valid CML representation
converted this representation to a CDK AtomContainer
assigned 2-D coordinates
rendered a PNG image in color

Notice how the thiaazabicyclo[3.2.0] system, complete with properly-placed substitutents, was flawlessly identified and parsed.

If you entered the above test code interactively via IRB, you may have noticed a multi-second delay in instantiating Depictor. This latency results from a sluggish NameToStructure constructor in OPSIN. A similar delay also occurs in OPSIN's pure-Java unit tests. Once Depictor is instantiated, however, image generation occurs relatively quickly.

The unususal orientation of the beta-lactam carbonyl group is determined by CDK's StructureDiagramGenerator. The source of this behavior will be explored in a future article.

More Examples

To illustrate some of the capabilities of the OPSIN-RCDK combination, a few more examples are provided below.

One of OPSIN's more surprising features is how well it handles heterocycles. For example, the IUPAC name for caffeine (1,3,7-trimethylpurine-2,6-dione) is translated to:

As another example, consider the tetrazole (1-[2-hydroxy-3-propyl-4-[3-(2H-tetrazol-5-yl)propoxy]phenyl]ethanone):

Highly substituted benzene rings and carboxylic acids are also translated accurately, as in 3-acetamido-5-(acetyl-methyl-amino)-2,4,6-triiodo-benzoic acid (Metrizoate):

How about a hairy-looking macrocycle name with multiple levels of morpheme nesting (3,6-diamino-N-[[15-amino-11-(2-amino-3,4,5,6-tetrahydropyrimidin-4-yl)-8- [(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo- 1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide)? Not a problem:

Limitations

In my tests of the OPSIN library, one structure appeared to be incorrectly parsed - N-(5-chloro-2-methyl-phenyl)-2-methoxy-N-(2-oxooxazolidin-3-yl)acetamide:

There are actually two problems with the output. First, an oxygen atom and a methyl group are overlapping near the top of the diargram. This cosmetic issue is related to CDK's StructureDiagramGenerator. Second, the oxazolidine nitrogen atom is misplaced by OPSIN. The correct 2-D image of this molecule, obtained from PubChem, is shown below:

Conclusions

It's not common to find an early-development Open Source project with the sophistication of OPSIN. The smooth handling of nested morphemes, aromatic heterocycles, macrocycles, and a good fraction of what I threw at it leads me to belive that a well-designed and extensible nomenclature parsing engine lies at OPSIN's core. More on that later, though.

What could you do with a powerful Open Source IUPAC nomenclature parser? The answer to that one question could fill a three-volume series. Suffice it to say that OPSIN, in combination with other Open Source software, offers virtually limitless potential for indexing, collecting, repackaging, reprocessing, and mashing up vast amounts of chemical information. Because of its Open Source license, OPSIN can be extended and otherwise modified to fit your particular needs. Future articles will highlight some of the possibilities.