WEBnm@ v2.0: Web server and services for comparing protein flexibility

Abstract

BackgroundNormal mode analysis (NMA) using elastic network models is a reliable and cost-effective computational method to characterise protein flexibility and by extension, their dynamics. Further insight into the dynamics–function relationship can be gained by comparing protein motions between protein homologs and functional classifications. This can be achieved by comparing normal modes obtained from sets of evolutionary related proteins.ResultsWe have developed an automated tool for comparative NMA of a set of pre-aligned protein structures. The user can submit a sequence alignment in the FASTA format and the corresponding coordinate files in the Protein Data Bank (PDB) format. The computed normalised squared atomic fluctuations and atomic deformation energies of the submitted structures can be easily compared on graphs provided by the web user interface. The web server provides pairwise comparison of the dynamics of all proteins included in the submitted set using two measures: the Root Mean Squared Inner Product and the Bhattacharyya Coefficient. The Comparative Analysis has been implemented on our web server for NMA, WEBnm@, which also provides recently upgraded functionality for NMA of single protein structures. This includes new visualisations of protein motion, visualisation of inter-residue correlations and the analysis of conformational change using the overlap analysis. In addition, programmatic access to WEBnm@ is now available through a SOAP-based web service. Webnm@ is available at http://apps.cbu.uib.no/webnma.ConclusionWEBnm@ v2.0 is an online tool offering unique capability for comparative NMA on multiple protein structures. Along with a convenient web interface, powerful computing resources, and several methods for mode analyses, WEBnm@ facilitates the assessment of protein flexibility within protein families and superfamilies. These analyses can give a good view of how the structures move and how the flexibility is conserved over the different structures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0427-6) contains supplementary material, which is available to authorized users.

Comparative Normal Mode Analysis of the Dynamics of DENV and ZIKV Capsids

“…In this paper, we have described an implementation of normal mode analysis based on elastic network models that enables such analyses. This implementation is based on the known foundations in the domain (Tirion, 1996) and does not deviate significantly from other available implementations (Zheng and Doniach, 2003; Suhre and Sanejouand, 2004; Kruger et al, 2012; Tiwari et al, 2014; Eyal et al, 2015; Frappier et al, 2015). We discuss in details its parametrization, namely the choice of the coarse graining of the molecular system, the choice of the method for computing the elastic network, and the assignment of force constants to the resulting springs, and justify the choices we have implemented.…”

“…During the past few years, several web-servers performing on-line Normal Mode Analysis (NMA) have been set up and described: ElNemo (Suhre and Sanejouand, 2004), ENCoM (Frappier et al, 2015), Webnm@ (Tiwari et al, 2014), ANM 2.0 (Eyal et al, 2015), AD-ENM (Zheng and Doniach, 2003), NMSim (Kruger et al, 2012). We have extended and updated our own server, NOMAD-REF (Lindahl et al, 2006), with a new and user-friendlier interface, including a better visual representation of the results while at the same time enlarging the performances of the core calculation of Normal Modes in the framework of the ENM representation.…”

The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity

“…Trajectory data from the simulations were recorded and analyzed in VMD [54]. Normal modes were calculated with the WEBnm@ program [55] using the default parameters and Cα atoms of the MLL5 protein. WEBnm@ uses the elastic network model and calculates the six lowest-frequency vibrational modes (modes 7–12).…”

Normal mode analysis as a method to derive protein dynamics information from the Protein Data Bank

“…This makes it possible to systematically perform NMA for many PDB structures. Using this advantage, several databases and online servers delivering NMA have been developed to reveal the dynamic features of proteins (Echols et al 2003;Suhre and Sanejouand 2004;Wako et al 2004;Yang et al 2005Yang et al , 2006Skjaerven et al 2014;Tiwari et al 2014;Eyal et al 2015). ProMode, ProMode-Oligomer, and ProModeElastic are examples of such databases developed by the authors (Wako et al 2004;Endo 2012, 2013).…”