Can proteins and crystals self-catalyze methyl rotations?

Area of Science:

• Computational chemistry
• Structural biology
• Biophysics

Background:

• The chi (C(alpha)-C(beta)) torsional barrier is crucial for understanding molecular flexibility.
• The influence of the surrounding environment on these barriers is not fully understood.

Purpose of the Study:

• To investigate the chi torsional barrier in alanine dipeptide crystals.
• To explore the role of the crystal environment in catalyzing rotation around the chi dihedral angle.
• To assess the relevance of this effect in biological structures.

Main Methods:

• Ab initio calculations at various levels of theory.
• Molecular mechanics and molecular dynamics simulations.
• Pharmacophore model screening of the Protein Data Bank.

Main Results:

• Crystal environment significantly reduces the chi torsional barrier in alanine dipeptide (N-methyl-l-alanyl-N-methylamide) by up to approximately 2kT compared to the gas phase.
• This catalytic effect, driven by van der Waals interactions, is present at both low and room temperatures.
• A similar reduction in the chi torsional barrier was observed in an alanine residue within a protein at low temperatures, but not at room temperature.

Conclusions:

• Environment-catalyzed rotation of methyl groups occurs in both crystalline solids and native biological structures.
• The observed catalytic effect is temperature-dependent, suggesting its significance may vary with biological conditions.
• This phenomenon could contribute to the low-frequency vibrational modes of molecules in biological systems.