- Technical Note
- Open Access
EasyModeller: A graphical interface to MODELLER
© Reddanna et al; licensee BioMed Central Ltd. 2010
- Received: 30 January 2010
- Accepted: 16 August 2010
- Published: 16 August 2010
MODELLER is a program for automated protein Homology Modeling. It is one of the most widely used tool for homology or comparative modeling of protein three-dimensional structures, but most users find it a bit difficult to start with MODELLER as it is command line based and requires knowledge of basic Python scripting to use it efficiently.
The study was designed with an aim to develop of "EasyModeller" tool as a frontend graphical interface to MODELLER using Perl/Tk, which can be used as a standalone tool in windows platform with MODELLER and Python preinstalled. It helps inexperienced users to perform modeling, assessment, visualization, and optimization of protein models in a simple and straightforward way.
EasyModeller provides a graphical straight forward interface and functions as a stand-alone tool which can be used in a standard personal computer with Microsoft Windows as the operating system.
- Protein Data Bank
- Template Structure
- Loop Modeling
- Protein Data Bank File
- Chain Information
Structural information of biological macromolecules is readily available in the Protein Data Bank (PDB) , http://www.pdb.org. By Sep 2009, the PDB contained ~ 60,713 experimental protein structures that can be grouped into ~ 3500 families . Considering that the number of non redundant amino acid sequence entries is around 408,000 http://www.expasy.org/sprot/, there is a huge gap between known annotated sequences and available 3 D structures. Developments in genomics have also spurred the developments in X-ray crystallography and NMR techniques to solve the new protein structure, which in turn has widened their use in drug discovery . However, these efforts are no where near in solving the 3 D structures of all the known proteins in any system. In the absence of experimental structures, computational methods are used to predict 3 D protein models to provide insight into the structure and function of these proteins. The steps involved in this process are : (1) identification of homolog that can be used as template(s) for modeling; (2) alignment of the target sequence to the template(s); (3) backbone generation; (4) loop modeling; (5) side-chain modeling; (6) model optimization; and (7) validation of the model. Repositories like The SWISS-MODEL http://swissmodel.expasy.org/SWISS-MODEL.html, Protein Model Portal http://proteinmodelportal.org and Modbase http://modbase.compbio.ucsf.edu, contain protein models generated using various auto-mated methods. However, without human intervention, errors as a result of inaccurate sequence alignment, and inability to identify and correctly model domains, such as loop and ligand-binding regions, are magnified, which results in the generation of low-accuracy models and thus limiting their applicability to drug discovery projects [7, 8]. In this context, the development of various user friendly and accurate tools for homology modeling is an active area of research such as new recent tools like HHPRED and Modeller at http://toolkit.tuebingen.mpg.de/sections/tertstruct toolkit, GeneSilico https://genesilico.pl/toolkit/[9–15]. MODELLER is one of the most widely used tools for homology or comparative modeling of protein three-dimensional structures. MODELLER stands apart from other packages due to its free availability, powerful features and reliable results. But most users find a bit difficult to start with MODELLER as it is command line based. Hence a freely available GUI for MODELLER would thus be very helpful to exploit the powers and advantages of this package more effectively. EasyModeller is a graphical user interface to MODELLER program.
The GUI eliminates the requirement of prior knowledge in the backend applications, thereby increasing the number of users of MODELLER and assists them to exploit the unique features of this great package more effectively. EasyModeller uses default parameters for most commands during software execution to make the process as simple as possible. User can change the parameters manually by editing the associated python script file (*.py) generated in the working directory.
EasyModeller will be updated by adding features like comparison and manual combination of multiple template structure and manual definition of spatial restraints into a more powerful GUI to MODELLER which could simultaneously display both alignment and structure windows, and have them interact with each other.
Project name: EasyModeller
Project homepage: http://www.uohyd.ernet.in/modellergui/
Operating system: Microsoft Windows (any)
Programming language: Perl (using Perl/Tk)
Other requirements: The system must have MODELLER (any version will work but preferably the latest version to get the best results) and Python (2.5 or 2.6 and not 3.11) preinstalled in the default installation directory (C://Program files/..). If the operating system is Windows Vista or Windows 7 then please run the executable file (.exe) of EasyModeller with administrative privilege (by right clicking it and selecting "Run as administrator"). Since EasyModeller uses the Microsoft Excel plot function to plot the profile graph, it is necessary to have Microsoft Excel installed in the system. A PDB viewer like Rasmol is required to visualize the generated model.
License: Free to use
Any restrictions to use by non-academics: None
We thank Centre for Modelling, Simulation and Design (CMSD), University of Hyderabad for the computational facilities. We duly acknowledge Council of Scientific and Industrial Research (CSIR), Govt. of India for providing senior research fellowship to PA and UGC for providing GATE fellowship to BKK.
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000, 28 (1): 235-242. 10.1093/nar/28.1.235.PubMed CentralPubMedView ArticleGoogle Scholar
- Cavasotto CN, Phatak SS: Homology modeling in drug discovery: current trends and applications. Drug Discov Today. 2009, 14 (13-14): 676-683. 10.1016/j.drudis.2009.04.006.PubMedView ArticleGoogle Scholar
- Manjasetty BA, Turnbull AP, Panjikar S, Bussow K, Chance MR: Automated technologies and novel techniques to accelerate protein crystallography for structural genomics. Proteomics. 2008, 8 (4): 612-625. 10.1002/pmic.200700687.PubMedView ArticleGoogle Scholar
- Krieger E, Nabuurs SB, Vriend G: Homology modeling. Methods Biochem Anal. 2003, 44: 509-523.PubMedGoogle Scholar
- Arnold K, Kiefer F, Kopp J, Battey JN, Podvinec M, Westbrook JD, Berman HM, Bordoli L, Schwede T: The Protein Model Portal. J Struct Funct Genomics. 2009, 10 (1): 1-8. 10.1007/s10969-008-9048-5.PubMed CentralPubMedView ArticleGoogle Scholar
- Pieper U, Eswar N, Davis FP, Braberg H, Madhusudhan MS, Rossi A, Marti-Renom M, Karchin R, Webb BM, Eramian D: MODBASE: a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res. 2006, D291-295. 10.1093/nar/gkj059. 34 DatabaseGoogle Scholar
- Dalton JA, Jackson RM: An evaluation of automated homology modelling methods at low target template sequence similarity. Bioinformatics. 2007, 23 (15): 1901-1908. 10.1093/bioinformatics/btm262.PubMedView ArticleGoogle Scholar
- Venclovas C, Margelevicius M: The use of automatic tools and human expertise in template-based modeling of CASP8 target proteins. Proteins. 2009, 77 (Suppl 9): 81-88. 10.1002/prot.22515.PubMedView ArticleGoogle Scholar
- Sali A, Blundell TL: Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993, 234 (3): 779-815. 10.1006/jmbi.1993.1626.PubMedView ArticleGoogle Scholar
- Fiser A, Do RK, Sali A: Modeling of loops in protein structures. Protein Sci. 2000, 9 (9): 1753-1773. 10.1110/ps.9.9.1753.PubMed CentralPubMedView ArticleGoogle Scholar
- Hildebrand A, Remmert M, Biegert A, Soding J: Fast and accurate automatic structure prediction with HHpred. Proteins. 2009, 77: 128-132. 10.1002/prot.22499.PubMedView ArticleGoogle Scholar
- Soding J, Biegert A, Lupas AN: The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 2005, W244-248. 10.1093/nar/gki408. 33 Web ServerGoogle Scholar
- Battey JN, Kopp J, Bordoli L, Read RJ, Clarke ND, Schwede T: Automated server predictions in CASP7. Proteins. 2007, 69 (Suppl 8): 68-82. 10.1002/prot.21761.PubMedView ArticleGoogle Scholar
- Dunbrack RL: Sequence comparison and protein structure prediction. Curr Opin Struct Biol. 2006, 16 (3): 374-384. 10.1016/j.sbi.2006.05.006.PubMedView ArticleGoogle Scholar
- Fiser A, Sali A: Modeller: generation and refinement of homology-based protein structure models. Methods Enzymol. 2003, 374: 461-491. full_text.PubMedView ArticleGoogle Scholar
- Hall TA: Bioedit: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/nt. Nucleic Acids Symposium Series. 1999, 41: 95-98.Google Scholar
- Sayle RA, Milner-White EJ: RASMOL: biomolecular graphics for all. Trends Biochem Sci. 1995, 20 (9): 374-10.1016/S0968-0004(00)89080-5.PubMedView ArticleGoogle Scholar
- Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE: UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004, 25 (13): 1605-1612. 10.1002/jcc.20084.PubMedView ArticleGoogle Scholar
- Humphrey W, Dalke A, Schulten K: VMD: visual molecular dynamics. J Mol Graph. 1996, 14 (1): 33-38. 10.1016/0263-7855(96)00018-5. 27-38PubMedView ArticleGoogle Scholar
- Shen MY, Sali A: Statistical potential for assessment and prediction of protein structures. Protein Sci. 2006, 15 (11): 2507-2524. 10.1110/ps.062416606.PubMed CentralPubMedView ArticleGoogle Scholar
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