Theoretical spectroscopy of floppy peptides at room temperature. A DFTMD perspective: gas and aqueous phase

Theoretical spectroscopy is mandatory for a precise understanding and assignment of experimental spectra recorded at finite temperature. We review here room temperature DFT-based molecular dynamics simulations for the purpose of interpreting finite temperature infrared spectra of peptides of increasing size and complexity, in terms of temperature-dependent conformational dynamics and flexibility, and vibrational anharmonicities (potential energy surface anharmonicities, vibrational mode couplings and dipole anharmonicities). We take examples from our research projects in order to illustrate the main key-points and strengths of dynamical spectra modeling in that context. The calculations are presented in relation to room temperature gas phase IR-MPD experiments and room temperature liquid phase IR absorption experiments. These illustrations of floppy polypeptides have been chosen in order to convey the following ideas: temperature-dependent spectra modeling is pivotal for a precise understanding of gas phase spectra recorded at room temperature, including conformational dynamics and vibrational anharmonicities; harmonic spectroscopy (as commonly performed in the literature) can be misleading and even erroneous for a proper interpretation of spectra recorded at finite temperature; taking into account vibrational anharmonicities is pivotal for a proper interplay between theory and experiments; amide I-III bands are not necessarily the most relevant fingerprints for unraveling the local structures of peptides and more complex systems; liquid phase simulations have unraveled relationships between the zwitterionic properties of the peptide bonds and infrared signatures. The review presents a state-of-the-art account of the domain and offers perspectives and new developments for future still more challenging applications.