Shared Signature Dynamics Tempered by Local Fluctuations Enables Fold Adaptability and Specificity

Area of Science:

• Evolutionary biology
• Structural biology
• Computational biology

Background:

• Protein function is linked to sequence, structure, and dynamics.
• Understanding how protein dynamics contribute to functional differentiation and evolution is key.

Purpose of the Study:

• To investigate the role of protein dynamics in the evolution of protein families and subfamilies.
• To develop a computational method for analyzing protein dynamics across large datasets.

Main Methods:

• Systematic computational analysis of 26,899 proteins from 116 CATH superfamilies.
• Introduction of SignDy, an integrated pipeline using elastic network models to evaluate signature dynamics.
• Characterization of cooperative mechanisms and convergent/divergent dynamics within protein families.

Main Results:

• Family members share conserved, cooperative global motions.
• A subset of low-to-intermediate frequency motions distinguishes subfamilies and is crucial for functional differentiation.
• High-frequency motions are conserved but minimally collective, contrasting with global motions.

Conclusions:

• Modulation of conserved global dynamics by specific low-frequency fluctuations is a versatile mechanism for protein adaptability and subfamily specificity.
• SignDy provides a dynamics-based categorization for understanding subfamily mechanisms beyond sequence or structure.
• Protein dynamics play a significant role in evolutionary diversification and functional specialization.