Backbone conformational preferences and pseudorotational ring puckering of 1-aminocyclopentane-1-carboxylic acid.

We have used quantum mechanical calculations at the B3LYP/6-311G(d,p) level to determine the conformational preferences of the N-acetyl-N'-methylamide derivative of 1-aminocyclopentane-1-carboxylic acid in the gas phase, chloroform solution, and water solution. The backbone conformation of this dipeptide has been described through the dihedral angles varphi and psi, while the pseudorotational phase angle was used to define the conformation of the cyclopentane ring. Results indicate that the backbone flexibility of this amino acid is restricted by the cyclic nature of the side chain, the relative stability of the different conformations depending on the polarity of the environment. The potential energy of the pseudorotation was also studied as a function of the backbone conformation. Interestingly, the conformation of the cyclic side chain depends on the backbone arrangement. Furthermore, the number of pseudorotational states accessible at room temperature is high in all the investigated environments, especially in aqueous solution. Finally, a set of force-field parameters for classical molecular mechanics calculations was developed for the investigated amino acid. Molecular dynamics simulations in both chloroform and aqueous solutions were performed to demonstrate the reliability of such parameters.