Proteins are highly dynamic molecules, whose function is intrinsically linked to these molecular motions. Many pathogenic and drug resistant mutations exerting phenotypic effects through changes in protein conformation and flexibility. Understanding these dynamic motions is therefore essential to characterise the molecular consequences of genomic variants. Despite this, most approaches for assessing the impact of mutations rely upon static primary or tertiary structures, due to the computational costs associated with Molecular Dynamic based approaches.
To fill this gap, here we report, DynaMut, a user friendly web server that combines two distinct well established normal mode approaches together with graph based signatures, to rapidly analyse protein dynamics by sampling conformations. DynaMut provides simplified dynamics analysis through principal component analysis, visualization of modes of motions and residue correlation mapping revealing correlated and anti-correlated regions of any given protein structure, and providing access to geometrically realistic conformational ensembles. In addition, DynaMut also enables rapid analysis of the impact of mutations on a protein’s dynamics and stability resulting from vibrational entropy changes, alongside with visual comparison of the interatomic interactions, atomic fluctuation and deformation energies between wild-type and mutant structures. Integration of the different approaches into a consensus prediction provided a much more accurate assessment of the impact of a mutation on protein stability. Finally, a set of useful .
DynaMut has been developed to be simple to use for non-technical users, providing rapid and simplified access to powerful and insightful analysis of protein motions. All resources generated during analysis and predictions by DynaMut can also be downloaded for further use. The web server is freely available at http://biosig.unimelb.edu.au/dynamut/.