How many hydrogen-bonded α-turns are possible?

Area of Science:

• Computational Chemistry
• Structural Biology
• Biophysics

Background:

• Alpha-turns are five-amino acid structures that reverse peptide sequence direction.
• Hydrogen bonding plays a critical role in stabilizing peptide conformations.

Purpose of the Study:

• To systematically analyze the conformational possibilities of isolated alpha-turns.
• To investigate the role of the i to i+4 hydrogen bond in alpha-turn stability.
• To compare computational findings with experimentally observed structures in the Protein Data Bank.

Main Methods:

• Ab initio molecular orbital (MO) theory calculations were employed.
• Calculations were performed in vacuum (HF/6-31G*, B3LYP/6-311+G*) and in solution (CPCM/HF/6-31G*).
• Conformational analysis focused on structures with a hydrogen bond between the first and fifth amino acid.

Main Results:

• Few alpha-turn structures, particularly with glycine and alanine, met the geometric criteria for the i to i+4 hydrogen bond.
• The most stable computed alpha-turns align with structures found in the Protein Data Bank.
• Smaller pseudocycles (beta- and gamma-turns) showed a tendency to form additional hydrogen bonds, sometimes disrupting the i to i+4 bond.
• An "ideal" alpha-turn, mimicking alpha-helix backbone angles, was not localized due to competing interactions.

Conclusions:

• Isolated alpha-turns with a strong i to i+4 hydrogen bond are uncommon.
• The stability of alpha-turns is influenced by competition with other hydrogen bonding patterns, such as those found in beta- and gamma-turns.
• While hints of stable alpha-turns exist without the i to i+4 hydrogen bond, their formation is less favored.