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

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Proteins function through structural changes, often driven by the movement of quasi-rigid domains.
• Understanding these domains is key to characterizing protein mechanics and biological function.

Purpose of the Study:

• To present SPECTRUS, a novel computational scheme for robustly identifying intrinsic quasi-rigid domains in proteins and large complexes.
• To demonstrate the utility of amino acid distance fluctuations for domain identification.

Main Methods:

• SPECTRUS utilizes fluctuations in amino acid distances to pinpoint quasi-rigid domains.
• The method is validated using both pairs of representative structures and large ensembles of conformers.
• The approach is applied to diverse biomolecular systems, including kinases, ion channels, and viral capsids.

Main Results:

• SPECTRUS consistently identifies functionally relevant quasi-rigid domains across various protein types and sizes.
• The identified domains effectively capture the essential degrees of freedom governing protein structural dynamics.
• Functional insights into protein mechanisms are gained through domain decomposition.

Conclusions:

• SPECTRUS offers a general and robust method for identifying quasi-rigid protein domains from structural data.
• The tool aids in understanding protein mechanics and functional dynamics.
• SPECTRUS is available as a software package and web server for broader scientific use.