Quantum mechanical study of secondary structure formation in protected dipeptides

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Dipeptides are fundamental units in protein structure.
• Understanding peptide conformation is crucial for drug design and protein folding studies.
• Side chain bulk influences peptide backbone structure.

Purpose of the Study:

• To computationally investigate the conformational preferences of three capped dipeptides: Ac-Gly-Phe-NH(2), Ac-Ala-Phe-NH(2), and Ac-Val-Phe-NH(2).
• To identify the stable conformers of these dipeptides using advanced theoretical methods.
• To compare computational findings with experimental observations, particularly regarding the impact of side chain bulk.

Main Methods:

• Local second-order Møller-Plesset perturbation theory (LMP2) calculations.
• Density Functional Theory (DFT) computations.
• Conformational analysis of capped dipeptides.

Main Results:

• Identified experimentally observed conformers for Ac-Gly-Phe-NH(2) and Ac-Ala-Phe-NH(2) as gamma(L)-gamma(L)(g-) and beta-turn I(g+).
• Identified closely related conformers, gamma(L)(g+)-gamma(L)(g-) and beta-turn I(a,g+), for Ac-Val-Phe-NH(2).
• The minimum energy structure for Ac-Val-Phe-NH(2) was found to be a beta-strand, contradicting experimental propensity for beta-turns in bulky peptides.

Conclusions:

• Computational methods accurately predict experimentally observed peptide conformations.
• The study highlights that bulky side chains do not necessarily favor beta-turns.
• The minimum energy conformation for Ac-Val-Phe-NH(2) is a beta-strand, a structure not detected experimentally, suggesting a potential discrepancy between computational predictions and experimental conditions for bulky peptides.