Vibrational spectroscopy modeling of a drug in molecular solvents and enzymes

•The IR lineshape of the CN stretch of a drug in different environments is studied.•Frequency-frequency correlations times are computed and compared with experiments.•Theoretical modeling of the IR lineshapes works only on homogeneous environments.

Modeling of drugs in enzymes is of immensurable value to many areas of science. We present a theoretical study on the vibrational spectroscopy of Rilpivirine, a HIV reverse transcriptase inhibitor, in conventional solvents and in clinically relevant enzymes. The study is based on vibrational spectroscopy modeling of the drug using molecular dynamics simulations, DFT frequency maps, and theory. The modeling of the infrared lineshape shows good agreement with experimental data for the drug in molecular solvents where the local environment motions define the vibrational band lineshape. On the other hand, the theoretical description of the drug in the different enzymes does not match previous experimental findings indicating that the utilized methodology might not apply to heterogeneous environments. Our findings show that the lack of reproducibility might be associated with the development of the frequency map which does not contain all of the possible interactions observed in such systems.

Graphical abstractDownload high-res image (158KB)Download full-size image