SPECTRUS: A Dimensionality Reduction Approach for Identifying Dynamical Domains in Protein Complexes from Limited Structural Datasets

Identifying dynamical, quasi-rigid domains in proteins provides a powerful means for characterizing functionally oriented structural changes via a parsimonious set of degrees of freedom. In fact, the relative displacements of few dynamical domains usually suffice to rationalize the mechanics underpinning biological functionality in proteins and can even be exploited for structure determination or refinement purposes. Here we present SPECTRUS, a general scheme that, by solely using amino acid distance fluctuations, can pinpoint the innate quasi-rigid domains of single proteins or large complexes in a robust way. Consistent domains are usually obtained by using either a pair of representative structures or thousands of conformers. The functional insights offered by the approach are illustrated for biomolecular systems of very different size and complexity such as kinases, ion channels, and viral capsids. The decomposition tool is available as a software package and web server at spectrus.sissa.it. [Display omitted] •SPECTRUS is a general method for identifying dynamical domains in proteins•It performs spectral clustering of amino acids based on their distance fluctuations•It takes as input conformers from PDB entries or MD trajectories•The SPECTRUS web server and source code are available at spectrus.sissa.it Ponzoni et al. present SPECTRUS, a general method to identify dynamical domains in proteins. SPECTRUS uses a dimensional reduction of the inter-residue distance fluctuations and exploits its properties to single out the intrinsic number and type of domains.