First steps in growth of a polypeptide toward β-sheet structure

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Modeling

Background:

• Beta-sheet formation is crucial for protein structure and function.
• Understanding initial peptide chain interactions is key to modeling protein folding.
• Dipeptides exhibit specific conformational preferences, including ring structures.

Purpose of the Study:

• To model the initial steps of beta-sheet formation using a dipeptide system.
• To investigate conformational changes in a dipeptide due to interactions with a second peptide chain.
• To identify the role of interpeptide interactions and hydrogen bonds in stabilizing conformations.

Main Methods:

• Computational examination of the full conformational energy surface of a model molecule.
• Comparison of the model molecule's surface with the geometrical preferences of an isolated dipeptide.
• Analysis of perturbations induced by interpeptide strand interactions.

Main Results:

• Interpeptide interactions eliminate the C5 ring structure's stability in the dipeptide.
• A C7 structure remains the global minimum, but its stability relies on interpeptide hydrogen bonds (NH···O and CH···O).
• Secondary and tertiary minima are also influenced by CH···O hydrogen bonds.
• A two-strand beta-sheet structure was not observed in this small model system.

Conclusions:

• Interpeptide interactions significantly alter dipeptide conformational landscapes.
• Hydrogen bonds, including non-canonical CH···O interactions, play a vital role in stabilizing peptide conformations.
• Larger peptide systems are required to form stable two-strand beta-sheet structures.