- Open Access
Molecular structure input on the web
Journal of Cheminformatics volume 2, Article number: 1 (2010)
A molecule editor, that is program for input and editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. This review focuses on a special type of molecule editors, namely those that are used for molecule structure input on the web. Scientific computing is now moving more and more in the direction of web services and cloud computing, with servers scattered all around the Internet. Thus a web browser has become the universal scientific user interface, and a tool to edit molecules directly within the web browser is essential.
A program for the input and editing of molecules is an indispensable part of every cheminformatics or molecular processing system. Such a program is known as a molecule editor, molecular editor or structure sketcher. Its function is to facilitate entry of molecules or reactions into an computer with help of mouse and keyboard actions. There are two types of molecule editors: 3D editors, supporting creation of 3D molecular structures, mainly for use in molecular modeling applications, and 2D editors generating "flat" 2D molecule representations used as input to various molecular processing services, such as searches of chemical databases or the creation of chemical illustrations.
In this overview only 2D molecule editors used for chemical structure input on the web will be covered. The World Wide Web, introduced originally as a medium for exchange of scientific information, is affecting now practically all aspects of our life, but scientific and technical applications still benefit proportionally more from the web technology. Scientific computing is moving more and more in the direction of web services and cloud computing, with servers scattered all around the Internet, and the web browser becoming the universal scientific user interface. Chemistry is no exception from this trend and input of molecular structures directly within a web browser is therefore of utmost importance.
Early web-based structure input tools
The first web-based molecular processing tools did not have capability to enter molecule structures graphically, because the early web technology allowed only input of textual data. Users were therefore asked to input their molecules as SMILES strings  or to upload structure files created with help of locally installed molecule drawing programs. Several ingenious web developers tried to overcome this limitation by offering character-based or image-based construction of molecules from fragments, but these systems were not easy to use and therefore did not find general acceptance. Example of such an interesting system which allows construction of molecules from ASCII characters is still functional at the Dundee PRODRG2 modelling server  (Figure 1).
The first "true" web structure editor, which allowed creation and modification of molecules directly within a web page was developed at Ciba-Geigy (later Novartis) as part of the in-house web-based cheminformatics system  (Figure 2). This editor was based on so called "clickable map" technology. The structure to be modified was displayed on the web page as an image. The user had to select the required editing action from a menu and then click the atom or bond that should be modified. The click coordinates, together with the desired action, were sent to the server, where the structure was modified and a new molecular image was sent back. The disadvantage of this approach was that for every structural change, the program required a new connection to the server, where a native application had to be launched before responding to the client. Despite this, the editor was a huge step forward from previous text-only entry, enabling relatively easy interactive input of molecules on the web by medicinal chemists and it boosted the use of interactive cheminformatics services on the Ciba-Geigy intranet. This editor become direct inspiration to the Daylight GRINS editor  (Figure 3) based on the same principle.
Introduction of the Java programming language in 1995 contributed considerably to increased interactivity of web applications. Small graphical Java programs - applets - could be integrated directly into web pages to add practically any desired functionality. Probably the first molecule editor in Java was an applet written by D. Bayada from the Leeds University. Source code of this program was available and one can still find it on the Internet . Independently a JME molecule editor applet was implemented at Ciba-Geigy (later Novartis). Many other molecule editor applets have been subsequently developed and currently some 20 such programs can be found on the Internet (Figure 4), differing considerably in their size, easy of use, development status and licensing. An incomplete list includes ACD/SDA , ChemWriter , Edit2D , ensochemEditor , ICedit , JavaGrins , JME , JUME , KegDraw , Marvin Sketch , Osiris  and Symyx JDraw . Additionally, several Java editors are available also in open source, including JChemPaint , JMolDraw , MCDL  and SketchEl , encouraging collaborative software development by the global cheminformatics community.
In the following section the JME Molecule Editor will be described in more details, as a representative example of this type of web-based structure input tools.
JME Molecule Editor
The JME Molecule Editor  is a Java applet which allows one to draw, edit, and display molecules and reactions directly within web page (Figure 5). The editor was originally written at Comenius University in Bratislava in QuickBASIC by author of this review and later translated into Java to be used as a structure input tool for an in-house web-based cheminformatics system at Ciba-Geigy and later at Novartis [5, 24]. Due to many requests, the JME editor has been released to the public and is currently probably the most popular molecular entry system on the web.
The JME editor is able to generate SMILES, MDL Molfile or its own compact format (one line textual representation of a molecule or reaction including also atomic 2D coordinates) of the input molecules. The SMILES code generated by JME is canonical, i.e. independent on the way how the molecule was drawn. The applet can also serve as a query input tool for searching molecular databases by supporting creation of complex substructure queries (Figure 6), which are automatically translated into SMARTS . With help of simple HTML form elements, the creation of 3D structure queries is also possible, as used for example in 3D pharmacophore searches in the NCI database system . Input of reactions is also supported (Figure 7), including generation of reaction SMILES and SMIRKS .
The JME applet is written in Java 1.0, the initial version of Java programming language. Java 1.0 does not support any sophisticated graphics or user interface elements, but on the other side, it is available in all types and versions of web browsers, therefore JME can run practically everywhere, without the need to rely on additional Java plugins (which are not always available). Another advantage of the simple architecture is the JME size (below 40 kB), which assures very fast loading in web pages. Thank to the Java platform independence, the JME runs on Windows PCs, Mac/OS machines and practically all UNIX clones, including, of course, LINUX.
The number of Internet sites which use the JME applet as a molecule input tool is too large to be listed here. These sites include molecular databases, property prediction services, various cheminformatics tools (such as generation of 3D structures, prediction of metabolic sites, combinatorial library design, or QSAR services just to name some) or interactive sites focused on chemistry education. Several such representative applications, which may be of general interest, have been collected here . For an additional review of free web tools focused on applications in medicinal chemistry and drug discovery, see review .
For non-commercial purposes, the JME Editor may be obtained directly from the author of this review.
Server Side Editors
Future of the Molecule Editing on the Web
Another technology for adding interactivity to web pages is Adobe Flash. Although currently used mostly for creating advertisements and video-streamimg applications, integrated scripting language called ActionScript also allows interactive drawing within web pages. To the authors knowledge, no molecule editor has been written in Flash, yet, but available chemical applications like chemical structure viewer , or crystal viewer , show that that Flash can be used to create nice interactive chemical applications. One can therefore expect that sooner or later, a molecule editor written in Flash will appear.
This short overview of history and current status of web-based structure input tools illustrates clearly that the web technology is evolving extremely quickly. New technologies, new tools and services are appearing almost daily. Web-based cheminformatics applications are following this trend. It is also gratifying to see the advent of open source movement in cheminformatics on the Internet, as advocated for example by the Blue Obelisk Group  and witnessed by collaborative projects like Chemistry Development Kit CDK , Jmol , Bioclipse  and several others. In this respect, cheminformatics seems to be closing the gap on the traditionally more open source world of bioinformatics. The future of cheminformatics, and particularly of cheminformatics applications on the web, is indeed exciting.
Gasteiger J, Engel T, (Eds): Chemoinformatics - A Textbook. 2003, Wiley-VCH, Weinheim, 137-155.
Gunda TE: Review of Chemical Drawing Programs. [http://dragon.klte.hu/~gundat/rajzprogramok/dprog.html]
Weininger D: SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. J Chem Inf Comput Sci. 1988, 28: 31-36. 10.1021/ci00057a005.
Dundee PRODRG2 Server. [http://davapc1.bioch.dundee.ac.uk/prodrg/]
Ertl P, Jacob O: WWW-based chemical information system. J Mol Struct (Theochem). 1997, 419: 113-120. 10.1016/S0166-1280(97)00179-6.
Daylight GRINS Editor. [http://www.daylight.com/daycgi/grins]
Molecule Editor_1_0. [http://www.ccl.net/cca/software/SOURCES/JAVA/MoleculeEditor/MoleculeEditor_1_0.java.html]
ACD/Structure Drawing Applet. [http://www.acdlabs.com/products/java/sda/]
JME Molecule Editor. [http://www.molinspiration.com/jme/index.html]
JUME Molecule Editor. [http://www.upstream.ch/products/topnmr_demo.html]
OSIRIS Property Explorer. [http://cheminformatics.ch/propertyExplorer/]
Krause S, Willighagen E, Steinbeck C: JChemPaint - Using the Collaborative Forces of the: 1 to Develop a Free Editor for 2D Chemical Structures. Molecules. 2000, 5: 93-98. 10.3390/50100093.
MCDL Editor. [http://sourceforge.net/projects/mcdl/]
Ertl P, Muehlbacher J, Rohde B, Selzer P: Web-based cheminformatics and molecular property prediction tools supporting drug design and development at Novartis. SAR QSAR Env Res. 2003, 14: 321-328. 10.1080/10629360310001673917.
SMARTS - A Language for Describing Molecular Patterns. [http://www.daylight.com/dayhtml/doc/theory/theory.smarts.html]
Enhanced NCI Database Browser, choose option Substructure and/or 3D Search. [http://cactvs.nci.nih.gov/ncidb2/]
SMIRKS - A Reaction Transform Language. [http://www.daylight.com/dayhtml/doc/theory/theory.smirks.html]
Ertl P, Rohde B, Selzer P: Fast calculation of molecular polar surface area directly from SMILES. Daylight European User Meetting, Cambridge, UK. 2000, [http://www.daylight.com/meetings/emug00/Ertl/index.html]
Interesting cheminformatics tools using the JME Editor. [http://peter-ertl.com/sites-using-jme-editor.html]
Ertl P, Jelfs S: Designing Drugs on the Internet? Free Web Tools and Services Supporting Medicinal Chemistry. Curr Top Med Chem. 2007, 7: 1491-1501. 10.2174/156802607782194707.
Ihlenfeld W-D, Bolton EB, Bryant SH: The PubChem Chemical Structure Sketcher. J Cheminf. 2009, 1: 20-10.1186/1758-2946-1-20.
The PubChem Project. [http://pubchem.ncbi.nlm.nih.gov/]
Molinspiration WebME Editor. [http://www.molinspiration.com/docu/webme/]
WebCME Editor. [http://pc.ardoino.com/pj-kem-molecular-editor/]
ChemDoodle Web Components. [http://web.chemdoodle.com/]
Flash Chemical 3D Structure Viewer. [http://www.javac.jp/flash/molecular/moleculardraw003/index.html]
3D Crystal Viewer. [http://www.dawgsdk.org/crystal/]
The Blue Obelisk. [http://blueobelisk.sourceforge.net/wiki/Main_Page]
The Chemistry Deveopment Kit (CDK). [http://sourceforge.net/apps/mediawiki/cdk/index.php?title=Main_Page]
I want to thank Richard Lewis for critically reading the manuscript and for helpful comments.
The author declares that they have no competing interests.
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Ertl, P. Molecular structure input on the web. J Cheminform 2, 1 (2010) doi:10.1186/1758-2946-2-1
- Drawing Program
- Canvas Element
- Blue Obelisk
- Molecule Editor
- Molecular Modeling Application