Intrinsic conformational characteristics of alpha,alpha-diphenylglycine

Quantum mechanical calculations at the B3LYP/6-31+ G(d, p) level have been used to investigate the intrinsic conformational preferences of alpha,alpha-diphenylglycine, a simple alpha,alpha-dialkylated amino acid bearing two phenyl substituents on the alpha-carbon, in both the gas phase and aqueous solution. Nine minimum energy conformations have been characterized for the N-acetyl-N'-methylamide derivative within a relative energy range of about 9 kcal/mol. The relative stability of these structures is largely influenced by specific backbone center dot center dot center dot side chain and side chain center dot center dot center dot side chain interactions that can be attractive (N-H center dot center dot center dot pi and C-H center dot center dot center dot center dot pi) or repulsive (C=O center dot center dot center dot pi). On the other hand, comparison with the minimum energy conformations calculated for alpha-aminoisobutyric acid, in which the two phenyl substituents are replaced by methyl groups, revealed that the bulky aromatic rings of alpha,alpha-diphenylglycine induce strain in the internal geometry of the peptide. Finally, a set of force-field parameters for classical Molecular Mechanics calculations was developed for the investigated amino acid. Molecular Dynamics simulations in aqueous solutions have been carried out to validate the parameters obtained.

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