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. (Chemical Equation Presented).
Original language | English |
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Pages (from-to) | 1350-1361 |
Number of pages | 12 |
Journal | Journal of Physical Chemistry B |
Volume | 119 |
Issue number | 4 |
Early online date | 12 Jan 2015 |
DOIs | |
Publication status | Published - 29 Jan 2015 |