PyMine: a PyMOL plugin to integrate and visualize data for drug discovery
© Chaudhari and Li. 2015
Received: 9 April 2015
Accepted: 21 September 2015
Published: 1 October 2015
Tremendous amount of chemical and biological data are being generated by various high-throughput biotechnologies that could facilitate modern drug discovery. However, lack of integration makes it very challenging for individual scientists to access and understand all the data related to a specific protein of interest.
To overcome this challenge, we developed PyMine, a PyMOL plugin that retrieves chemical, structural, pathway and other related biological data of a receptor and small molecules from a variety of high-quality databases and presents them in a graphic and uniformed way.
Developed as an interactive and user-friendly tool, PyMine can be used as a central data-hub for users to access and visualize multiple types of data and to generate new ideas intuitively for structure-based molecule design.
KeywordsPyMOL Data integration Data visualization Drug discovery
Big data generated by a variety of high-throughput biotechnologies have catalyzed the booming of chemoinformatics and bioinformatics databases. The recent database issue of the Nucleic Acid Research journal has collected 171 such actively maintained databases  and many of them are growing at an enormous rate . These databases cover various aspects of biological systems such as protein structures, functional sites, small-molecule ligands, and pathways etc., and thus are crucial for modern drug discovery. However, these data are stored in different databases and lack of data integration and visualization makes it challenging to effectively access and understand all the data in order to facilitate drug discovery processes . This is especially true for a biology scientist not trained in bioinformatics who wish to adventure into the drug design avenue in their investigations as basic drug discovery is increasingly shifting toward academic laboratories .
Several attempts have been reported to address this challenge. Cytoscape is an open source software platform for complex network visualization and data integration . UCSF Chimera is a molecular modeling program for visualization and analysis of molecular structures and related data . Both Cytoscape and Chimera are stand-alone software packages and were not developed exclusively for drug discovery purpose. Aquaria  and PDBpaint  were developed to retrieve features from various databases and map them onto the protein structures. Both programs focus primarily on structural features such secondary structures and domains. NsSNP Loader (http://vbc.med.monash.edu.au/~fauxn/pymol_plugin/plugin.html) is a PyMOL plugin that maps the non-synonymous single nucleotide polymorphism (nsSNP) data on the structure of the protein. The PDBbind database collects binding data for macromolecules and their ligands, and provides some basic display of protein–ligand complexes . Both NsSNP Loader and PDBbind, however, focus on a single type of biological data.
A unique PyMOL  plugin, PyMine was developed to provide a central data-hub that automatically retrieves multiple types of data directly related to drug discovery from various databases and present them in an easily understandable way. It also allows visualization of the protein 3D structure, ligand binding site, and single amino acid variation (SAV) information. Hence, through data integration and visualization, PyMine will provide a broader perspective on the drug discovery project in hand in a limited time frame to help generate new ideas for drug development. Along with other PyMOL plugin tools [11, 12], PyMine could be used as a platform to head start any drug discovery projects.
For data visualization, PyMine takes advantage of the 3D visualization module of PyMOL that makes it a unique tool to combine visualization of structural data along with presenting relevant biological information.
PyMine was written in python and is compatible with python versions 2.5.6 and above (Python Software Foundation, www.python.org). The GUI was created using Python’s native Tkinter library. For minimal dependence, no external python package/libraries were used. PyMine has been tested on Ubuntu 10.04.5 and Mac OS X 10.7.5 systems.
We developed PyMine to serve as a central data-hub that automatically retrieves chemical and biological data from multiple databases and presents them in an interactive and uniformed way. To illustrate the function of PyMine, we chose a wild-type protein of the BRAF oncoprotein with known structure (PDB ID: 4E26) as an example. The BRAF oncoprotein is found to be mutated in about half of malignant melanomas and other cancers, and is under intensive studies.
Through the 3D visualization module of PyMOL, the 3D structure of the BRAF protein was automatically loaded into the graphic window of PyMOL (Fig. 2b). In addition, available SAV and binding site information for the protein was retrieved and also mapped onto the 3D structure of the protein without any extra commands from the user. By toggling among the buttons provided on the right panel, users can selectively display certain information over others for visual study.
Along with visualization, PyMine also generated multiple output files containing information such as a list of FDA approved drugs and compounds studied in biochemical assays of the protein of interest and pathway map (Fig. 2c). These files were generated in the standard format and can be used directly for protein–ligand docking studies or network analyses.
Hundreds of biological databases of various types have been generated and many of them are growing rapidly [1, 2]. It is becoming increasingly challenging for an individual biological scientist to mine those databases manually and periodically in order to collect information related to the protein of their interest and to make sense of those data of different types such as protein structure, binding site, SAV, compound and pathway . To help alleviate the problems related to this challenge, we developed the PyMine software that automatically retrieves data from six major and comprehensive, chemical and biological databases so that users can access all the data using a single platform.
Using PyMine as a central data-hub will provide several advantages. First, the users don’t need to access those databases manually and individually since all data will be automatically retrieved. Second, the protein structure and its binding ligand will be automatically loaded into PyMOL’s graphic window with binding site and SAV data mapped onto the structure. Users can visually study them to understand the structural and functional impact of SAV and to develop new ideas about compound modification for structure-based molecular design. Further, Most of the information is outputted into text files in the standard format, which can be directly adopted for further computational studies.
In the current implementation, PyMine focuses on data extraction and visualization. No algorithms are developed and incorporated for further computational analyses such as structure comparison or protein–ligand docking. In addition, information contained in all the databases under consideration except for the PDB database are deposited based on the individual wild-type protein sequence. Therefore, the PDB ID or UniProt ID entered by a user should correspond to the wild-type sequence of the protein. Otherwise, most of the information won’t be retrieved and loaded.
Several efforts have been reported for data visualization and integration [5–9]. Compared to those software packages of similar purpose, PyMine was developed to automatically and exclusively retrieve multiple types of data that are directly related to drug discovery. In addition, PyMine is based on PyMOL, a free and broadly adopted graphic visualization software.
Overall, we reported here a PyMOL plugin that focuses on automatically collecting and integrating multiple types of data from various database sources. With the growth of both database number and size, we envision this plugin will be widely adopted by biological scientists with/without bioinformatics training. Furthermore, PyMine can be combined with other PyMOL plugins such as the Amber and AutoDockVina plugins for molecular dynamics simulations and protein–ligand docking , to provide an integrated platform for drug discovery. In the future, we plan to continuously improve PyMine by incorporating additional databases.
In summary, we proposed an innovative, easy to use PyMOL plugin that automatically retrieves chemical and biological data from six high-quality biological databases and presents them in an easy understandable way. Using a popular graphic software PyMOL, multiple types of data can be accessed easily without going through multiple databases manually. Users can instead focus on understanding those data and use the graphic tools to help develop new hypotheses.
Availability and requirements
Project name: PyMine.
Project home page: https://github.com/zhijunlilab/PyMine.
Operating system(s): Linux and Mac OS X.
Programming language: Python.
License: MIT license.
Any restriction to use by non-academics: license needed.
RC designed and programmed the software. ZL supported the project and provided guidance. RC and ZL co-drafted the manuscript. All authors read and approved the final manuscript.
We thank our anonymous reviewers for constructive comments. Research reported in this publication was supported in part by Grant Number UL1RR024134 from the National Center for Research Resources and in part by the Institute for Translational Medicine and Therapeutics’ (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics at University of Pennsylvania.
Compliance with ethical guidelines
Competing interests The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/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://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Galperin MY, et al. The 2015 nucleic acids research database issue and molecular biology database collection. Nucleic Acids Res. 2015;43(Database issue):D1–5.PubMed CentralView ArticlePubMedGoogle Scholar
- Joachimiak A. High-throughput crystallography for structural genomics. Curr Opin Struct Biol. 2009;19:573–84.PubMed CentralView ArticlePubMedGoogle Scholar
- Masseroli M, et al. Integrated Bio-Search: challenges and trends for the integration, search and comprehensive processing of biological information. BMC Bioinform. 2014;15(Suppl 1):S2. doi:https://doi.org/10.1186/1471-2105-15-S1-S2.View ArticleGoogle Scholar
- Silber BM. Driving drug discovery: the fundamental role of academic labs. Sci Transl Med. 2010;2(30):30cm16. doi:https://doi.org/10.1126/scitranslmed.3000169.PubMedGoogle Scholar
- Shannon P, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMed CentralView ArticlePubMedGoogle Scholar
- Pettersen EF, et al. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.View ArticlePubMedGoogle Scholar
- O’Donoghue SI, et al. Aquaria: simplifying discovery and insight from protein structures. Nat Methods. 2015;12(2):98–9.View ArticlePubMedGoogle Scholar
- Fournier D, Andrade-Navarro MA. PDBpaint, a visualization webservice to tag protein structures with sequence annotations. Bioinformatics. 2011;27(18):2605–6.PubMedGoogle Scholar
- Liu Z, et al. PDB-wide collection of binding data: current status of the PDBbind database. Bioinformatics. 2015;31(3):405–12.View ArticlePubMedGoogle Scholar
- DeLano WL. The PyMOL molecular graphics system. Schrödinger LLC wwwpymolorg, version 1. 2002. http://www.pymol.org.
- Bramucci E, et al. PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL. BMC Bioinform. 2012;13:S2. doi:https://doi.org/10.1186/1471-2105-13-S4-S2.View ArticleGoogle Scholar
- Lill MA, Danielson ML. Computer-aided drug design platform using PyMOL. J Comput Aided Mol Des. 2011;25:13–9.View ArticlePubMedGoogle Scholar
- The UniProt Consortium. UniProt: a hub for protein information. Nucleic Acids Res. 2015;43(Database issue):D204–12.PubMed CentralView ArticleGoogle Scholar
- Berman HM, et al. The Protein Data Bank. Nucleic Acids Res. 2000; 28:235–242.PubMed CentralView ArticlePubMedGoogle Scholar
- Gaulton A, et al. ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012;40(Database issue):D1100–7.PubMed CentralView ArticlePubMedGoogle Scholar
- Kanehisa M, et al. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 2014;42:D199–D205.PubMed CentralView ArticlePubMedGoogle Scholar
- Yip YL, et al. Annotating single amino acid polymorphisms in the UniProt/Swiss-Prot knowledgebase. Hum Mutat. 2008;29:361–6.View ArticlePubMedGoogle Scholar
- Shoemaker BA, et al. IBIS (Inferred Biomolecular Interaction Server) reports, predicts and integrates multiple types of conserved interactions for proteins. Nucleic Acids Res. 2012;40(Database issue):S834–40.View ArticleGoogle Scholar