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

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.

Figure 1

PyMod integrated tools flowchart. The workflow shows how the separate tools are integrated in PyMod. Each tool must be considered as standalone (e.g., it's possible to perform a sequence alignment task without searching in the database as a mandatory step).

Figure 2

PyMod main window. By using the main window, the user can perform almost all PyMod functions using the top menu or just operating on the sequences and their name.

Figure 3

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

Figure 4

Secondary structure colouring method. The user can color the protein sequences by their secondary structure or by the physicochemical properties of their amino acids. The secondary structure assignment is based on the proSS algorithm http://roselab.jhu.edu/utils/pross.html.

Figure 5

Homology model and quality assessment. Once homology models have been built, they are automatically loaded onto PyMOL and the user can assess the models quality through a graph constructed using the DOPE scoring function.