The Development Of Three-Dimensional Biological Relevant Spectrum Web Service

Our research group proposed a molecular descriptor based on molecular shape similarity vector---Three-Dimensional Biologically Relevant Spectrum(BRS-3D).BRS-3D can be used for ligand-based virtual screening,drugs combination and multi-target drugs discovery.However,due to the large amount of calculation on molecular shape comparison,real-time calculation cannot be realized,and the online computing platform of BRS-3D has not been established so far.This paper covered the steps of overall architecture design,technical route selection,frontend and backend development,deployment and test,finally completed the development of BRS-3D web service.BRS-3D web service can provide the query of user's target compound BRS-3D in nearly 1.7 million pre-calculated compounds BRS-3D results and single compound BRS-3D online calculation as well as molecular similarity search based on BRS-3D.The BRS-3D web service consists of five functional modules: the query of compound's BRS-3D,compound's BRS-3D online calculation,BRS-3D based molecular similarity search,sub-procedures scheduling and user management.a)Query of compound BRS-3D: Users can query in the pre-calculated BRS-3D database by submitting the Canonical SMILES of a given compound or directly uploading the 3D structure file in mol2 format.The result can be downloaded in CSV or JSON format.b)Compound BRS-3D online calculation: If the pre-calculated BRS-3D database does not contain the given compound,the user can submit an online calculation task of the compound BRS-3D.After the task is completed,the results will be returned via email.c)Molecular similarity search: Users can submit a molecular similarity search task by submitting a given compound and then setting similarity search parameters.After the task is completed,the two-dimensional structure of the analog of the given compound in mol2 format and the similarity score file,will be returned by mail.d)Task scheduling: The user's submitting task information will be written to the database.The system asynchronously executes a series of sub-processes for the tasks in the database by queue,and finally completes the established functions.e)User management: In the BRS-3D network service,user registration,mailbox verification,login and logout functions are implemented.The fronted part of BRS-3D web service was designed by Axure for prototype map,and was developed on the responsive layout of the Twitter Bootstrap framework,using Ajax technology to achieve frontend interaction.The backend business logic was written on the Node.js platform,and the implementation of each functions relied on a few of Node components,Python scripts,MongoDB databases,and high-performance computing cluster.The current version(v1.0.0)has been tested open to users on campus.The results showed that each functional module with friendly frontend interface could run normally and was easy to use.This web service not only facilitates the query and calculation of BRS-3D descriptors,but also provides a new research perspective for quantitative structure-activity relationship analysis and artificial intelligence-based drug discovery.At the same time,the BRS-3D database contains a large number of domestically purchasable compounds information,the potential active candidate compounds for optimization of lead compounds,"Me Too" drug design can be quickly discovered based on known active compounds.