title: Mechanism of stabilization of helix secondary structure by constrained Cα-tetrasubstituted α-amino acids.
abstract: The theoretical basis behind the ability of constrained Cα-tetrasubstituted amino acids (CTAAs) to induce stable helical conformations has been studied through Replica Exchange Molecular Dynamics Potential of Mean Force Quantum Theory of Atoms In Molecules calculations on Ac-l-Ala-CTAA-l-Ala-Aib-l-Ala-NHMe peptide models. We found that the origin of helix stabilization by CTAAs can be ascribed to at least two complementary mechanisms limiting the backbone conformational freedom: steric hindrance predominantly in the (+x,+y,-z) sector of a right-handed 3D Cartesian space, where the z axis coincides with the helical axis and the Cα of the CTAA lies on the +y axis (0,+y,0), and the establishment of additional and relatively strong C-H···O interactions involving the CTAA.
authors.affiliation: Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian, 21 20133 Milano, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Maffucci
authors.forename: Sara
authors.initials: S
authors.lastname: Pellegrino
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clayden
authors.forename: Alessandro
authors.initials: A
authors.lastname: Contini
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006860:Hydrogen Bonding; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids