Polyalanine α-helix microsolvation: assessing the energy of the peptide desolvation penalty with density functional theory

• Published in: Theoretical chemistry accounts 2016-09, Vol.135 (9), p.1-7, Article 220
• Main Author: Ireta, Joel
• Format: Article
• Language: English
• Subjects: Alanine; Atomic/Molecular Structure and Spectra; Bonding strength; Chemical bonds; Chemistry; Chemistry and Materials Science; Density functional theory; Festschrift in honour of A. Vela; Hydrogen bonds; Inorganic Chemistry; Organic Chemistry; Physical Chemistry; Polypeptides; Regular Article; Theoretical and Computational Chemistry; Water chemistry
• ISSN: 1432-881X; 1432-2234
• DOI: 10.1007/s00214-016-1981-y

To fold a solvated peptide into a helical conformation, water molecules solvating the peptide group must be removed before the formation of the helix-stabilizing backbone–backbone hydrogen bonds. The energy associated with such desolvation process, at 0 K, is assessed in this work investigating microsolvated infinitely long alanine polypeptides with density functional theory. It is shown that the energetic contribution of the desolvation penalty, at 0 K, disfavors the helix formation. Besides, it is found that the strength of backbone–backbone hydrogen bonds is not sufficiently large to compensate it. Still, strengthening of water–water hydrogen bonds along the microsolvation shell of the helix provides the extra energy needed to fully compensate the desolvation penalty, hence making the helix formation in aqueous solvent energetically favorable.