What Differentiates Free Amino Acids and Aminoacyl Residues? An Exploration of Conformational and Lipophilicity Spaces
Bernard Testa, Isabelle Raynaud, Lemont B. Kier · Helvetica Chimica Acta · 1999
The objective of this study was to unravel the changes in property space resulting from the amino-acid-to-residue transformation. Conformation-dependent lipophilicity was chosen as the metric to assess changes in property spaces. Phe, Ala-Phe-Ala, Gln, and Ala-Gln-Ala were first submitted to a conformational search strategy using quenched molecular dynamics in order to obtain an efficient sampling of a conformational space. This search was performed for the four electrical forms of the compounds (cationic, zwitterionic, uncharged, and anionic). The virtual lipophilicity (logP) of each conformer was then calculated by the Molecular Lipophilicity Potential (MLP). Similarly, the lipophilicity increment of the Phe and Gln residues in all electrical states and conformers of Ala-Phe-Ala and Ala-Gln-Ala, respectively, were calculated by the MLP. As expected, the results showed a marked expansion 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.