Kotov et al. J Cheminform (2018) 10:38 https://doi.org/10.1186/s13321-018-0292-9 SOFTWARE Open Access Chemotion‑ELN part 2: adaption of an embedded Ketcher editor to advanced research applications Serhii Kotov1,3, Pierre Tremouilhac1, Nicole Jung1,2* and Stefan Bräse1,2* Abstract The Ketcher editor, available as an Open Source software package for drawing chemical structures, has been expanded to include several features that allow storage, management and application of templates, as well as the use of symbols for a planning and processing of solid phase synthesis. In addition, tools for the drawing of coordinative bonds to represent e.g. organometallic compounds were added. The editor has been implemented into an Electronic Lab Notebook (ELN) application which enables the use of the Ketcher editor for advanced operations in chemistry research. The developments of the ELN-integrated Ketcher (ketcher-rails) support the retrieval of identifers and structure-related information from external databases and the molecule-based calculation of analytical values. The reworked editor can be used to generate molecular structures in reaction templates and to generate syntheses plans. Keywords: Molecule editor, Electronic Lab Journal, Open Source software, Ruby on Rails, JavaScript, Solid supports Background applications [4]. Te importance of ELN-integrated edi- Te defnition, storage and search of chemical informa- tors and the use of digital information management and tion in electronic laboratory notebooks (ELNs), databases storage over the whole research process is constantly or repositories depends on the availability of chemi- growing [1, 5, 6]. Especially the storage of reaction data cal editors to draw the molecular structures. Even the in machine readable formats (available via a processing of creation of chemical names and unique identifers, as a the drawings in molecule editors) has high impact as it prerequisite for the correlation of chemical data with can be used for the in silico calculation of new reaction descriptions or results, relies on the availability of elec- rules and the formation of reaction databases enriched tronic systems to input structural information [1, 2]. with research data [7–9]. In addition, molecule editors Chemical structure or molecule editors are necessary are very important to visualize chemical structures to for the processing of chemical structures in almost every improve their interpretation and understanding [10–13]. feld of chemical research, particularly in organic, inor- Several chemical structure editors have been developed ganic and polymer chemistry, and chemical biology. Tey in the past and are used in academia and industry. Chem- are used as standalone software for drawing molecular Draw developed by CambridgeSoft (now a product of structures in scientifc reports and manuscripts for the PerkinElmer) [14] and ISISDraw developed by MDL publication of research data. Moreover, they are also Information Systems (now a product of BIOVIA), are used as integrated systems [3] for fast and error-free among the most prominent editors [15]. Other examples processing of chemical information in diverse software of molecule editors are VectorMol (Sciformation) [16], JChemPaint [17], JSME [18], MarvinSketch (ChemAxon) [19], ChemSketch (ACD) [20], ChemDoodle (iChem- *Correspondence: [email protected]; [email protected] Labs) [21], and Ketcher (EPAM Life Sciences) [22]. In 1 Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, particular, the commercial editors, such as ChemDraw, Hermann‑von‑Helmholtz‑Platz 1, 76344 Eggenstein‑Leopoldshafen, Germany ofer a wide range of possible features which allow their Full list of author information is available at the end of the article use in many felds of chemistry research. However due © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kotov et al. J Cheminform (2018) 10:38 Page 2 of 8 to the unavailability of the source code for commercial used the established Ketcher 1.1 as Source Code, because software, adaptions of the molecule editor to the user’s Ketcher 2.0 is still in an alpha version (information taken needs are not possible, and the embedding and use of the from the provider EPAM) but we intend to upgrade our editor in a fexible (ELN) environment is limited. Both code to Ketcher 2.0 as soon as it is available as a stable arguments constrain the utility of the advanced commer- version. Our implementation of Ketcher and its integra- cial editors which reveals the need for continuous work tion into an ELN required a signifcant optimization and to improve Open Source software. Te Ketcher editor is rebuild as a Ruby software package (gem) called ketcher- one of the few developments that are available as Open rails. Tis allows easier embedding of Ketcher to any Source and ofers a strong basis of already implemented Rails application and also enables the use of numerous features for use in chemical research. Ketcher is a web- features of the Ruby on Rails framework. Many of our based molecule editor, written in JavaScript, providing developed functions beneft from the interaction of the options for stereochemistry support, standard 2D geom- ketcher-rails editor with chemotion-ELN which was pro- etry optimization (clean up), (de)aromatization, a list of grammed in Ruby, Javascript, HTML, and CSS. Te back- templates for cycles or chain functions, atom hotkeys and end server is built using the Ruby on Rails framework R-group labeling tools. Ketcher can import and export with PostgreSQL relational database, while the front-end molfle/rxnfle, as well as SMILES and supports scalable user interface is mainly constructed with the ReactJS vector graphics (SVG) or vector markup language (VML) framework to serve a single page application. Embed- for rendering [23]. Evaluating suitable molecule editors ding Ketcher into the Ruby software package allows it that would work on our current research projects, we to beneft from the fexibility of the ruby programming found Ketcher to be the most comprehensive, most fex- language. Additionally, embedding it into a web service ible and best documented Open Source software and that uses Ruby on Rails allows for the use of more fea- decided to use it as a basis for new developments. Addi- tures to improve the performance of the molecule editor tionally, the Ketcher editor can be used on tablets and signifcantly. Te embedded ketcher-rails uses the so- smartphones which allows more fexibility with diverse called Rails assets pipeline feature that can compile all devices. Te Ketcher editor is well established in the JavaScript and CSS fles into one fle and store it on the chemistry community and is ofered for search functions user’s computer until any of the fles are changed. Tis by e.g. Reaxys or ChemSpider [24]. It is also still under prevents unnecessary duplicate data transfer, and signif- (Open Source) development by the company EPAM [25] cantly improves performance, especially in network con- which will probably allow a merge of the achievements nections with low throughput and high latency. Te same of our development team with those of EPAM in future. procedure is applied to image fles that can be generated In this manuscript, our eforts towards the improvement and changed by the user, including the regeneration of of Ketcher editor as a modern and fexible Open Source the compiled image. Te technology used for images is 2D molecule editor are described. Tis work has resulted called “CSS sprites”. It is used to combine several images in an advanced molecule editor designed to fulfll the into one image and to render specifc partitions by CSS requirements of current chemical research with the addi- language. Terefore, multiple network requests for each tion of several new editing tools, while also ofering new image are reduced to a single request for a large image. features through its interaction in the environment of Te molecule editor is delivered as a Ruby software pack- an ELN. A prerequisite for such a benefcial symbiosis age which is easily integrated to any Ruby-on-Rails web is therefore the implementation of the molecule editor application. Ketcher-rails is a rails ‘engine’; it brings its into a fexible and powerful ELN, which was successfully own MVC components and DB tables into the main rails shown at the beginning of this project by embedding application. Te main function of an embedded molecule ketcher-rails into the Chemotion-ELN, a development of editor is the drawing of chemical structures which are our research group which has been reported earlier [26]. registered as molecules and can be used for any chemi- cal application managed by an ELN. For example, typical Implementation user cases include the creation of a chemical structure Te herein described developments base on the last sta- and its storage in the chemical database for commercial ble, well documented Open Source code of Ketcher (Ver- compounds, the use of a chemical structure to describe a sion 1.1-beta, formerly from GGA-software). A newer starting material, reagent or product of a chemical reac- version of Ketcher (Ketcher 2.0) is currently under tion or the defnition of a chemical structure as a sample development by the company EPAM [27] and will ofer placed for a biological investigation. Te procedure tak- several improvements in comparison to the original soft- ing place in the background during the registration of a ware, including the generation of user defned templates chemical structure as a molecule includes several steps.