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The infrared spectroscopy and dynamics of -CO labels in wild type and mutantinsulin monomer and dimer are characterized from molecular dynamics simulationsusing validated force fields. It is found that the spectroscopy of monomericand dimeric forms in the region of the amide-I vibration differs for residuesB24-B26 and D24-D26, which are involved in dimerization of the hormone. Also,the spectroscopic signatures change for mutations at position B24 fromphenylalanine - which is conserved in many organisms and known to play acentral role in insulin aggregation - to alanine or glycine. Using threedifferent methods to determine the frequency trajectories - solving the nuclearSchr\"odinger equation on an effective 1-dimensional potential energy curve,instantaneous normal modes, and using parametrized frequency maps - lead to thesame overall conclusions. The spectroscopic response of monomeric WT and mutantinsulin differs from that of their respective dimers and the spectroscopy ofthe two monomers in the dimer is also not identical. For the WT and F24A andF24G monomers spectroscopic shifts are found to be $\sim 20$ cm$^{-1}$ forresidues (B24 to B26) located at the dimerization interface. Although thecrystal structure of the dimer is that of a symmetric homodimer, dynamicallythe two monomers are not equivalent on the nanosecond time scale. Together withearlier work on the thermodynamic stability of the WT and the same mutants itis concluded that combining computational and experimental infraredspectroscopy provides a potentially powerful way to characterize theaggregation state and dimerization energy of modified insulins.

The Dynamics and Infrared Spectrocopy of Monomeric and Dimeric Wild Type and Mutant Insulin