From Infinite Helices to β Sheets: Structural Insights from Electronic Structure Calculations

Area of Science:

• Biophysics
• Computational Chemistry
• Protein Science

Background:

• Protein folding and aggregation involve helical and sheet conformations.
• The intrinsic energetics governing these structures are not fully understood.

Purpose of the Study:

• To characterize the conformational landscape of polyalanine using periodic density functional theory (DFT).
• To investigate the energetic balance between alpha-helices and beta-sheets in gas and aqueous phases.
• To understand the role of hydrogen bonding and solvation in protein secondary structure stability.

Main Methods:

• Periodic density functional theory (DFT) calculations at 0 K.
• Utilized infinite one- and two-dimensional models for polyalanine.
• Simulated both gas-phase and aqueous environments.

Main Results:

• Alpha-helices are favored in isolated polyalanine chains.
• Beta-sheet stability increases with the number of strands due to hydrogen-bond saturation.
• Solvation lowers energy barriers for helix-to-sheet transitions.

Conclusions:

• Beta sheets can be more stable than alpha-helices in extended structures, explaining their prevalence in amyloid and fibrous proteins.
• Periodic DFT is a valuable tool for studying protein secondary structure energetics in condensed phases.
• Findings provide insights into protein folding and misfolding mechanisms.