Ensembles from Ordered and Disordered Proteins Reveal Similar Structural Constraints during Evolution.

Area of Science:

• Protein structure and evolution
• Computational biology
• Biophysics

Background:

• Protein conformations are dictated by amino acid residue interactions.
• Evolutionary processes can impose structural constraints essential for protein function.
• Understanding these constraints is key to deciphering biological information encoded in protein sequences.

Purpose of the Study:

• To investigate the proportion of protein sites evolving under structural constraints.
• To compare these constraints in ordered and disordered protein ensembles.
• To analyze the evolutionary information content and redundancy in disordered protein ensembles.

Main Methods:

• Application of a structurally constrained model of protein evolution.
• Analysis of two distinct types of protein ensembles: ordered and disordered.
• Quantification of sites under structural constraints and their characteristics (e.g., long-range contacts).

Main Results:

• Both ordered and disordered protein ensembles exhibit comparable proportions (~40%) of sites under structural constraints.
• ~68% of constrained sites are located in disordered regions.
• Disordered ensembles demonstrate redundancy in evolutionary information, describable by an average of ~11 conformers.

Conclusions:

• Despite differences in complexity, protein ensembles show similar evolutionary pressures to maintain function.
• Structural constraints play a crucial role in preserving biological information across diverse protein types.
• Evolutionary information is vital for characterizing protein conformational ensembles.