Hydrophobic interactions and hydrogen bonds in β-sheet formation

Area of Science:

• Biophysics
• Computational Chemistry
• Protein Science

Background:

• Understanding peptide self-assembly into beta-sheet structures is crucial for comprehending protein folding and misfolding diseases.
• The role of interpeptide interactions and environmental factors in driving beta-sheet formation remains an active area of research.

Purpose of the Study:

• To investigate the driving forces behind beta-sheet formation in homodimeric peptides with varying side chain hydrophobicity.
• To elucidate the microscopic mechanisms governing peptide self-assembly using computational simulations.

Main Methods:

• All-atom molecular dynamics simulations were employed to study extended peptide conformations.
• A periodic boundary condition setup simulated infinitely long, stretched peptides.
• Potential of mean force calculations identified stable beta-sheet conformations.

Main Results:

• Homodimeric peptides formed beta-sheet structures at specific interpeptide distances (0.5 nm and 0.8 nm).
• Valine and leucine homodimers adopted cross-beta conformations with interpenetrating side chains.
• Beta-sheet formation was not correlated with the number of interpeptide hydrogen bonds but with electrostatic energy and system volume.

Conclusions:

• Hydrogen bonds do not appear to be the primary drivers of beta-sheet formation from extended conformations.
• Electrostatic interactions and the enthalpic penalty of water exclusion play significant roles.
• Microscopic mechanisms for beta-sheet formation differ between peptides with small and large hydrophobic side chains.