DynaMut is a web server using two distinct, well established normal mode approaches, which can be used to analyze and visualize protein dynamics by sampling conformations and assess the impact of mutations on protein dynamics and stability resulting from vibrational entropy changes. DynaMut integrates the graph-based signatures along with normal mode dynamics to generate a consensus prediction of the impact of a mutation on protein stability. DynaMut also provides a comprehensive suite for protein motion and flexibility analysis and visualization via a freely available, user friendly web server.
For protein dynamics analysis, the server requires the user to input a protein structure by either uploading a file in PDB format or by providing the four-letter accession code for any entry on the PDB database. In addition, users have the option to choose a specific force field, which is used to describe the molecular interactions within the structure for normal mode analysis.
Alternatively, for assessing the effects of mutations on protein dynamics and stability, two different input options are available. The ‘Single mutation’ option requires the user to provide a PDB file or PDB accession code, the point mutation specified as a string containing the wild-type residue one-letter code, its corresponding residue number and the mutant residue one-letter code. The ‘Mutation list’ option allows users to upload a list of mutations in a file for batch processing. For both input options the user is also asked to specify the chain identifier in which the wild-type residue is located.
In order to assist users to submit their jobs for analysis and predictions, sample submission entries are available in both submission pages and a help page is available via the top navigation bar.
For the analysis of protein dynamics, the results are displayed in four tabs. In the first tab, porcupine plots show the trajectory of movement. The second tab allows users to visualize the non-trivial modes generated, including an animated plot that describes the motion of the molecule. Visual representations of deformation energy and atomic fluctuation are displayed on the third tab. Finally, the last tab shows the cross-correlation between residue movements as both a correlation matrix and the 3D structure of the submitted protein.
The mutational analysis results are also split into tabs to enable users to easily navigate the different analyses available for evaluating the effects of mutations on protein stability and dynamics. For the ‘Single mutation’ option, the server outputs the predicted change in stability, along with the variation in entropy energy between wild-type and mutant structures in the first tab. For comparison purposes, in a separate panel the changes in stability calculated by structure-based methods are shown. DynaMut enables visualization of the non-covalent molecular interactions calculated by Arpeggio and deformation energies and atomic fluctuations of wild-type and mutant residues in their respective 3D structures. For the ‘Mutation list’ option, the server output is summarized as a downloadable table, and users have the option to analyze each mutation separately, similar to the analysis of a single mutation.