MODELLER and EasyModeller

Category Proteomics>Protein Structure/Modeling Systems/Tools

Abstract MODELLER is a computer program that models three-dimensional structures of proteins and their assemblies by satisfaction of spatial restraints.

MODELLER is most frequently used for homology or comparative protein structure modeling:

The user provides an alignment of a sequence to be modeled with known related structures and MODELLER will automatically calculate a model with all non-hydrogen atoms.

More generally, the inputs to the program are restraints on the spatial structure of the amino acid sequence(s) and ligands to be modeled. The output is a 3D structure that satisfies these restraints as well as possible.

Restraints can in principle be derived from a number of different sources.

These include related protein structures (comparative modeling), Nuclear Magnetic Resonance (NMR) experiments (NMR refinement), rules of secondary structure packing (combinatorial modeling), cross-linking experiments, fluorescence spectroscopy, image reconstruction in electron microscopy, site-directed mutagenesis, intuition, residue-residue and atom-atom potentials of mean force, etc.

The restraints can operate on distances, angles, dihedral angles, pairs of dihedral angles and some other spatial features defined by atoms or pseudo atoms.

Presently, MODELLER automatically derives the restraints only from the known related structures and their alignment with the target sequence.

A 3D model is obtained by optimization of a molecular probability density function (pdf). The molecular pdf for comparative modeling is optimized with the variable target function procedure in Cartesian space that employs methods of conjugate gradients and molecular dynamics with simulated annealing.

MODELLER can also perform multiple comparisons of protein sequences and/or structures, clustering of proteins, and searching of sequence databases.

MODELLER is used with a scripting language and does Not include any graphics.

EasyModeller --

EasyModeller is a front-end graphical interface tool to MODELLER using Perl/Tk [Perl is a programming language/Tk is a Graphical User Interface (GUI) toolkit], which can be used as a standalone tool on the Windows platform with MODELLER and Python preinstalled (Python is an interpreted, interactive, object-oriented, extensible programming language).

EasyModeller helps inexperienced users to perform modeling, assessment, visualization, and optimization of protein models in a simple and straightforward way.

EasyModeller is a standalone tool with a very intuitive interface which clearly defines the different steps of homology modeling. The tool consists of six (6) steps required for building a homology model.

1) The first step involves specifying the working directory, which is the folder location where the output files will be generated. This working directory will also help to keep a track of all the generated files.

2) The second and most basic step is entering the amino acid sequence information as the input parameter.

3) The third step is providing the template information to the program. The user can load the template structure(s) in standard formats like (.pdb, .ent, etc.) acceptable in MODELLER by using the Load template(s) feature.

The basic template information such as, its name, chains, heteroatoms, etc. are shown in the display area and the CHAIN is automatically set to default to the first chain as set in the Protein Data Bank (PDB) file.

To use a different chain for the template the text box containing the chain information can be edited and the desired chain id can be entered. The text box is automatically kept blank if No chain information is found.

To do multi template based modeling users can load all the template structure files one by one in order, with a maximum of six templates.

4) The next step of homology modeling is aligning the query sequence with the template which is achieved in step four.

The “Perform Alignment” feature aligns the query sequence with the template(s) using the “align2 d function” of MODELLER and displays the output alignment in the text display window of the tool.

A beneficial feature of this tool is the possibility to view and manually improve the query alignment via the feature “Edit Alignment”.

Although the tool provides a preliminary option for alignment editing, for users who would like to use advanced visual alignment editing, they can install BioEdit (a user-friendly biological sequence alignment editor and analysis program for Windows) and manually open the appropriate alignment (.ali) files from the current working directory with BioEdit.

5) The fifth step is generating the homology model by using the information generated so far. The “Generate Model” feature is used to achieve this by using the appropriate MODELLER function as required.

As soon as the model is generated, the best model is displayed in the users default PDB viewer such as Rasmol.

The generated model can be improved upon by loop modeling. MODELLER has several loop optimization methods, which all rely on scoring functions and optimization protocols adapted for loop modeling.

6) The sixth and the final step is model optimization which can be achieved by using the advanced optimization options. The various parameters for optimization and dynamics like temperature and number of iterations can be changed by editing the default value in the corresponding text boxes.

The minimized models are generated and are saved in the working directory inside a new folder called optimized models.

The dynamics output binary trajectory files are also saved in the same folder which can be read in by visualization software such as CHIMERA; or

VMD - (VMD is a molecular graphics program designed for the display and analysis of molecular assemblies, in particular biopolymers such as proteins and nucleic acids).

Furthermore, the model profile plot can be generated by selecting the “Plot profile of a model” option which calculates Discrete Optimized Protein Energy (DOPE) energy of the loaded model using the assess dope function.

EasyModeller 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. Users 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(s) and manual definition of spatial restraints into a more advanced GUI to MODELLER which could simultaneously display both alignment and structure windows, and have them interact with each other.

System Requirements

MODELLER is written in standard FORTRAN 90 and will run on UNIX, Windows, or Mac computers.

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.

Note: Refer to the instructions/requirements in the EasyModeller download package.




Manufacturer Web Site

MODELLER, EasyModeller (paper)

Price Contact manufacturer(s).

G6G Abstract Number 20718

G6G Manufacturer Number 104287