Infrared line shape of an α-carbon deuterium-labeled amino acid

The viability of α-carbon deuterated bonds (C_α-D) as infrared (IR) probes of protein backbone dynamics was explored through a combination of experiment and theory. α-Carbon deuterated alanine (Ala-d1) served as a convenient model system for a comparison of experiment, density functional theory (DFT), and combined quantum mechanical/molecular mechanical (QM/MM) simulations of the C_α-D IR line shape. In addition to the primary C_α-D absorption, the experimental spectrum contains three features that likely result from Fermi resonances. DFT calculations supported the assignments and identified the lower frequency modes participating in the Fermi resonances. A QM/MM simulation of the Ala-d₁ line shape was in qualitative agreement with the experiment, including the presence of classical analogues of Fermi resonances. These studies demonstrated that the C_α-D line shape is sensitive, via Fermi resonances, to lower frequency collective vibrations that are expected to play a role in protein dynamics and function, and that the QM/MM approach, which is applicable to proteins, is capable of aiding in their interpretation.