What differentiates free amino acids and aminoacyl residues? An exploration of conformational and lipophilicity spaces

The objective of this study was to unravel the changes in property space re sulting from the amino-acid-to-residue transformation. Conformation-depende nt lipophilicity was chosen as the metric to assess changes in property spa ces. Phe, Ala-Phe-Ala. Gin, and Ala-Gln-Ala were first submitted to a confo rmational search strategy using quenched molecular dynamics in order to obt ain an efficient sampling of a conformational space. This search was perfor med for the four electrical forms of the compounds (cationic, zwitterionic, uncharged, and anionic). The virtual lipophilicity (logP) of each conforme r was then calculated by the Molecular Lipophilicity Potential (MLP). Simil arly, the lipophilicity increment of the Phr and Gin residues in all electr ical states and conformers of Ala-Phr-Ala and Ala-Gln-Ala. respectively, we re calculated by the MLP. As expected, the results showed a marked expansio n in the property space of a tripeptide compared to an amino acid. However, they also revealed a marked reduction in property space resulting from the amino-acid-to-residue transformation.