WEBnm@: a web application for normal mode analyses of proteins

Abstract

Background: Normal mode analysis (NMA) has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes) describe the largest movements in a protein and are the ones that are functionally relevant.

Results: We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on http://www.bioinfo.no/tools/normalmodes. We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example.

Conclusion: We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains.

Figure 1

WEBnm@ architecture. a. The main page of WEBnm@ is a form where users can input a structure file in the PDB format. b. The server consists of two parts, the graphical web interface and the core of the program, written in Python, which performs the actual computation. The two parts communicate via a web application server, BIAZ.

Figure 2

Snapshots of an example calculation of the SERCA1 Ca-ATPase. a. Presentation of the 10 lowest frequency modes with their average deformation energy. b. Page presenting the available analyses. c. Page where user can choose the orientation of the system for the animations. d. Apparition of an icon on the page presenting the list of analyses. e. Page displaying animated gif image of the first 6 modes (7 to 12). f. List of analyses page after that both mode animations and atomic displacements have been calculated, two icons are present.

Figure 3

Normalized atomic displacements plots. Plots for modes 7 to 12 are generated on the same page and converted to a PDF file.