Modeling Nonaqueous Proton Wires Built from Helical Peptides: Biased Proton Transfer Driven by Helical Dipoles

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 116; no. 4; pp. 1283 - 1288
• Main Authors: López, Gustavo E, Colón-Díaz, Inara, Cruz, Anthony, Ghosh, Sumana, Nicholls, Samantha B, Viswanathan, Usha, Hardy, Jeanne A, Auerbach, Scott M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02-02-2012
• Subjects: A: Molecular Structure, Quantum Chemistry, General Theory; Amino acids; Barriers; Electronic structure; Helical; Models, Molecular; Networks; Peptides; Peptides - chemistry; Protein Structure, Secondary; Protons; Quantum Theory; Scaffolds; Wire
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp210208m

We report gas-phase electronic structure calculations on helical peptides that act as scaffolds for imidazole-based hydrogen-bonding networks (proton wires). We have modeled various 21-residue polyalanine peptides substituted at regular intervals with histidines (imidazole-bearing amino acids), using a hybrid approach with a semiempirical method (AM1) for peptide scaffolds and density functional theory (B3LYP) for proton wires. We have computed energy landscapes including barriers for Grotthuss-shuttling-type proton motions though wires supported on 310-, α- and π-helical structures, showing the 310- and α-helices to be attractive targets in terms of high proton affinities, low Grotthuss shuttling barriers, and high stabilities. Moreover, bias forces provided by the helical dipole moments were found to promote unidirectional proton translocation.