iPBAvizu: a PyMOL plugin for an efficient 3D protein structure superimposition approach

Abstract

Background: Protein 3D structure is the support of its function. Comparison of 3D protein structures provides insight on their evolution and their functional specificities and can be done efficiently via protein structure superimposition analysis. Multiple approaches have been developed to perform such task and are often based on structural superimposition deduced from sequence alignment, which does not take into account structural features. Our methodology is based on the use of a Structural Alphabet (SA), i.e. a library of 3D local protein prototypes able to approximate protein backbone. The interest of a SA is to translate into 1D sequences into the 3D structures.

Results: We used Protein blocks (PB), a widely used SA consisting of 16 prototypes, each representing a conformation of the pentapeptide skeleton defined in terms of dihedral angles. Proteins are described using PB from which we have previously developed a sequence alignment procedure based on dynamic programming with a dedicated PB Substitution Matrix. We improved the procedure with a specific two-step search: (i) very similar regions are selected using very high weights and aligned, and (ii) the alignment is completed (if possible) with less stringent parameters. Our approach, iPBA, has shown to perform better than other available tools in benchmark tests. To facilitate the usage of iPBA, we designed and implemented iPBAvizu, a plugin for PyMOL that allows users to run iPBA in an easy way and analyse protein superimpositions.

Conclusions: iPBAvizu is an implementation of iPBA within the well-known and widely used PyMOL software. iPBAvizu enables to generate iPBA alignments, create and interactively explore structural superimposition, and assess the quality of the protein alignments.

Keywords: Protein superimposition; Structural alignment; Structural alphabet; Structural bioinformatics; Visualisation.

Fig. 1

Example of iPBAvizu usage. (a) Two proteins, with lengths of 531 and 533 residues respectively are loaded into PyMOL (PDB code: 3GWD and 1W4X respectively); the structural superimposition is made using iPBAvizu. Arrows show the position of Amino acid and Protein Block sequence. This independent window contains the sequence alignment in terms of residues and PBs with different scores. It allows an interactive selection between the sequences and the structures. In the right panel are shown the two loaded proteins, then the two superimposed chains (the prefix iPBA_ is added before their names) and finally a select case, this last is not necessary but for some PyMOL versions must be shown (please do not interact with it without necessity). (b) and (c) show the selection of a protein fragment and rendering when a specific color is chosen