Non-classical Non-covalent σ-Hole Interactions in Protein Structure and Function: Concepts for Potential Protein...

Area of Science:

• Biochemistry
• Chemical Biology
• Structural Biology

Background:

• Biological molecule structure and function rely on noncovalent interactions, historically dominated by hydrogen bonds (H-bonds).
• The σ-hole concept revealed diverse nonclassical noncovalent (ncNC) interactions beyond H-bonds, expanding applications in chemistry and biochemistry.
• Halogen, chalcogen, and tetrel bonds are key ncNC interactions with significant electrostatic potential.

Purpose of the Study:

• To review the impact of halogen, chalcogen, and tetrel bonds on peptide and protein structure, assembly, and function.
• To highlight how these ncNC interactions can guide the design of novel functional proteins.
• To explore the potential of synergistic ncNC interactions, such as H-bond enhanced X-bonds, in protein engineering.

Main Methods:

• Review of existing literature on ncNC interactions in biological systems.
• Analysis of natural and synthetic examples of halogen, chalcogen, and tetrel bonds in peptides and proteins.
• Focus on studies demonstrating principles of stability, assembly, and catalysis mediated by these interactions.

Main Results:

• Halogen, chalcogen, and tetrel bonds are integral to protein structure and function, comparable in energy to H-bonds.
• These ncNC interactions play crucial roles in molecular recognition and the design of biomolecular assemblies.
• Synergistic effects, like H-bond enhanced X-bonds, demonstrate potential for fine-tuning protein properties.

Conclusions:

• Nonclassical noncovalent interactions are critical for understanding and designing protein stability, assembly, and catalysis.
• The σ-hole concept provides a framework for utilizing a broader range of noncovalent interactions in protein engineering.
• Exploiting synergistic ncNC interactions offers promising strategies for developing advanced functional proteins.