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PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL.

Bramucci E, Paiardini A, Bossa F, Pascarella S - BMC Bioinformatics (2012)

Bottom Line: A simple and intuitive interface, PyMod, between the popular molecular graphics system PyMOL and several other tools (i.e., [PSI-]BLAST, ClustalW, MUSCLE, CEalign and MODELLER) has been developed, to show how the integration of the individual steps required for homology modeling and sequence/structure analysis within the PyMOL framework can hugely simplify these tasks.Sequence similarity searches, multiple sequence and structural alignments generation and editing, and even the possibility to merge sequence and structure alignments have been implemented in PyMod, with the aim of creating a simple, yet powerful tool for sequence and structure analysis and building of homology models.PyMod represents a new tool for the analysis and the manipulation of protein sequences and structures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dipartimento di Scienze Biochimiche A, Rossi Fanelli, Sapienza Università di Roma, Roma 00185, Italy.

ABSTRACT

Background: In recent years, an exponential growing number of tools for protein sequence analysis, editing and modeling tasks have been put at the disposal of the scientific community. Despite the vast majority of these tools have been released as open source software, their deep learning curves often discourages even the most experienced users.

Results: A simple and intuitive interface, PyMod, between the popular molecular graphics system PyMOL and several other tools (i.e., [PSI-]BLAST, ClustalW, MUSCLE, CEalign and MODELLER) has been developed, to show how the integration of the individual steps required for homology modeling and sequence/structure analysis within the PyMOL framework can hugely simplify these tasks. Sequence similarity searches, multiple sequence and structural alignments generation and editing, and even the possibility to merge sequence and structure alignments have been implemented in PyMod, with the aim of creating a simple, yet powerful tool for sequence and structure analysis and building of homology models.

Conclusions: PyMod represents a new tool for the analysis and the manipulation of protein sequences and structures. The ease of use, integration with many sequence retrieving and alignment tools and PyMOL, one of the most used molecular visualization system, are the key features of this tool.Source code, installation instructions, video tutorials and a user's guide are freely available at the URL http://schubert.bio.uniroma1.it/pymod/index.html.

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Preferences window. The user can change many parameters of the tools implemented in PyMod through specific Options windows.
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Figure 3: Preferences window. The user can change many parameters of the tools implemented in PyMod through specific Options windows.

Mentions: PyMod can input and output sequences and 3D-structures in the popular FASTA and PDB formats. In the latter case, 3D-coordinates are automatically split in single chains, loaded into PyMOL, and their corresponding sequences loaded into the PyMod main window (Figure 2). After a sequence has been loaded onto the PyMod main window, users can search different databases, in order to retrieve protein sequences and related structures that are homologous to the query sequence, by means of the BLAST and PSI-BLAST search tools. BLAST is relatively faster while less sensitive when compared with profile-profile alignment methods. However, it can still detect homology with significant sequence identity (i.e., identity > 40%) [8,13,14], thus providing fast and useful means in the case of high identity, template-based modeling. On the other hand, PSI-BLAST, the most used profile-sequence alignment method, is more sensitive than sequence-sequence alignment and it can recognize distant homology with lower sequence identity (i.e., identity > 20%) [8]. Both tools have been therefore implemented in PyMod. Profile-profile alignments or HMM-HMM (Hidden Markov Models) comparison algorithms [15] may be the most effective approaches and even able to create accurate alignments in extreme cases (i.e., identity < 10%) [16], but they're usually much more complex and slower than sequence-sequence or profile-sequence alignments. Most notably, at these levels of sequence identity (0-20%), fold-recognition or ab initio approaches may be favored over homology modeling, for which PyMod flowchart has been primarily planned. PyMod includes support for running BLAST remotely (no local database installation is required) and PSI-BLAST locally. In the latter case, users are provided with the option to install local sequence databases, while PyMod provides a graphical interface to ease their use. To facilitate template structure search for homology modeling tasks, PyMod will be distributed with a pre-installed PDB sequence database, which will be updated in future releases on a monthly base. A number of (PSI-)BLAST parameters can be controlled by the user from within an apposite PyMod window (e.g., number of PSI-BLAST iterations, E-value threshold, % identity threshold) (Figure 3). Users are provided with the ability to select the (PSI-)BLAST results to be imported in the PyMod main window, by choosing from a table reporting the name of the retrieved sequences, their E-value and sequence identity. Selected sequences, once imported in PyMod, are automatically grouped in a separate cluster, which can be collapsed or contracted by simply clicking a button beside the query sequence. When searching the PDB database the user can retrieve the 3D-coordinates that are related to a selected query and automatically load the structure into the PyMOL main window.


PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL.

Bramucci E, Paiardini A, Bossa F, Pascarella S - BMC Bioinformatics (2012)

Preferences window. The user can change many parameters of the tools implemented in PyMod through specific Options windows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3303726&req=5

Figure 3: Preferences window. The user can change many parameters of the tools implemented in PyMod through specific Options windows.
Mentions: PyMod can input and output sequences and 3D-structures in the popular FASTA and PDB formats. In the latter case, 3D-coordinates are automatically split in single chains, loaded into PyMOL, and their corresponding sequences loaded into the PyMod main window (Figure 2). After a sequence has been loaded onto the PyMod main window, users can search different databases, in order to retrieve protein sequences and related structures that are homologous to the query sequence, by means of the BLAST and PSI-BLAST search tools. BLAST is relatively faster while less sensitive when compared with profile-profile alignment methods. However, it can still detect homology with significant sequence identity (i.e., identity > 40%) [8,13,14], thus providing fast and useful means in the case of high identity, template-based modeling. On the other hand, PSI-BLAST, the most used profile-sequence alignment method, is more sensitive than sequence-sequence alignment and it can recognize distant homology with lower sequence identity (i.e., identity > 20%) [8]. Both tools have been therefore implemented in PyMod. Profile-profile alignments or HMM-HMM (Hidden Markov Models) comparison algorithms [15] may be the most effective approaches and even able to create accurate alignments in extreme cases (i.e., identity < 10%) [16], but they're usually much more complex and slower than sequence-sequence or profile-sequence alignments. Most notably, at these levels of sequence identity (0-20%), fold-recognition or ab initio approaches may be favored over homology modeling, for which PyMod flowchart has been primarily planned. PyMod includes support for running BLAST remotely (no local database installation is required) and PSI-BLAST locally. In the latter case, users are provided with the option to install local sequence databases, while PyMod provides a graphical interface to ease their use. To facilitate template structure search for homology modeling tasks, PyMod will be distributed with a pre-installed PDB sequence database, which will be updated in future releases on a monthly base. A number of (PSI-)BLAST parameters can be controlled by the user from within an apposite PyMod window (e.g., number of PSI-BLAST iterations, E-value threshold, % identity threshold) (Figure 3). Users are provided with the ability to select the (PSI-)BLAST results to be imported in the PyMod main window, by choosing from a table reporting the name of the retrieved sequences, their E-value and sequence identity. Selected sequences, once imported in PyMod, are automatically grouped in a separate cluster, which can be collapsed or contracted by simply clicking a button beside the query sequence. When searching the PDB database the user can retrieve the 3D-coordinates that are related to a selected query and automatically load the structure into the PyMOL main window.

Bottom Line: A simple and intuitive interface, PyMod, between the popular molecular graphics system PyMOL and several other tools (i.e., [PSI-]BLAST, ClustalW, MUSCLE, CEalign and MODELLER) has been developed, to show how the integration of the individual steps required for homology modeling and sequence/structure analysis within the PyMOL framework can hugely simplify these tasks.Sequence similarity searches, multiple sequence and structural alignments generation and editing, and even the possibility to merge sequence and structure alignments have been implemented in PyMod, with the aim of creating a simple, yet powerful tool for sequence and structure analysis and building of homology models.PyMod represents a new tool for the analysis and the manipulation of protein sequences and structures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dipartimento di Scienze Biochimiche A, Rossi Fanelli, Sapienza Università di Roma, Roma 00185, Italy.

ABSTRACT

Background: In recent years, an exponential growing number of tools for protein sequence analysis, editing and modeling tasks have been put at the disposal of the scientific community. Despite the vast majority of these tools have been released as open source software, their deep learning curves often discourages even the most experienced users.

Results: A simple and intuitive interface, PyMod, between the popular molecular graphics system PyMOL and several other tools (i.e., [PSI-]BLAST, ClustalW, MUSCLE, CEalign and MODELLER) has been developed, to show how the integration of the individual steps required for homology modeling and sequence/structure analysis within the PyMOL framework can hugely simplify these tasks. Sequence similarity searches, multiple sequence and structural alignments generation and editing, and even the possibility to merge sequence and structure alignments have been implemented in PyMod, with the aim of creating a simple, yet powerful tool for sequence and structure analysis and building of homology models.

Conclusions: PyMod represents a new tool for the analysis and the manipulation of protein sequences and structures. The ease of use, integration with many sequence retrieving and alignment tools and PyMOL, one of the most used molecular visualization system, are the key features of this tool.Source code, installation instructions, video tutorials and a user's guide are freely available at the URL http://schubert.bio.uniroma1.it/pymod/index.html.

Show MeSH