Computational Peptidology Assisted by Conceptual Density Functional Theory for the Study of Five New Antifungal Tripeptides

A well-behaved model chemistry previously validated for the study of the chemical reactivity of peptides was considered for the calculation of the molecular properties and structures of a group of five new antifungal tripeptides, namely (2R)-2-[(2S)-2-[(2S)-2-amino-3-phenylpropanamido]propanamido]-5-[(diaminomethylidene)amino]pentanoic acid, (2S)-2-[(2S)-2-[(2S)-2-amino-3-phenyl propanamido]propanamido]-3-(4-hydroxyphenyl)propanoic acid, (2S)-2-[(2S)-2-[(2S)-2-amino-3-phenylpropanamido]-3-methylbutanamido]-3-(4-hydroxyphenyl)propanoic acid, (2R)-2-[(2S)-2-[(2S)-2-amino-3-phenylpropanamido]-3-(1H-indol-3-yl)propanamido]-3-sulfanylpropanoic acid, and (2S)-2-[(2S)-2-[(2S)-2-amino-3-phenylpropanamido]-3-(1H-indol-3-yl)propanamido]-3-(4-hydroxyphenyl)propanoic acid, according to their amino acid sequences. A methodology based on conceptual density functional theory was chosen for the determination of the reactivity descriptors. The molecular active sites were associated with the active regions of the molecules that were associated with the nucleophilic, electrophilic, and radical Fukui functions. Additionally, the pKa values for the different peptides are predicted with great accuracy, which constitutes a useful knowledge for the process of drug design. Finally, the bioactivity scores for the new antifungal peptides are predicted through a homology methodology relating them with the calculated reactivity descriptors.