title: Molecules-in-molecules fragment-based method for the calculation of chiroptical spectra of large molecules: Vibrational circular dichroism and Raman optical activity spectra of alanine polypeptides.
abstract: The molecules-in-molecules (MIM) fragment-based method has recently been adapted to evaluate the chiroptical (vibrational circular dichroism [VCD] and Raman optical activity [ROA]) spectra of large molecules such as peptides. In the MIM-VCD and MIM-ROA methods, the relevant higher energy derivatives of the parent molecule are assembled from the corresponding derivatives of smaller fragment subsystems. In addition, the missing long-range interfragment interactions are accounted at a computationally less expensive level of theory (MIM2). In this work we employed the MIM-VCD and MIM-ROA fragment-based methods to explore the evolution of the chiroptical spectroscopic characteristics of 310-helix, α-helix, β-hairpin, γ-turn, and β-extended conformers of gas phase polyalanine (chain length n = 6-14). The different conformers of polyalanine show distinctive features in the MIM chiroptical spectra and the associated spectral intensities increase with evolution of system size. For a better understanding the site-specific effects on the vibrational spectra, isotopic substitutions were also performed employing the MIM method. An increasing redshift with the number of isotopically labeled13C=O functional groups in the peptide molecule was seen. For larger polypeptides, we implemented the two-step-MIM model to circumvent the high computational expense associated with the evaluation of chiroptical spectra at a high level of theory using large basis sets. The chiroptical spectra of α-(alanine)20polypeptide obtained using the two-step-MIM model, including continuum solvation effects, show good agreement with the full calculations and experiment. This benchmark study suggests that the MIM-fragment approach can assist in predicting and interpreting chiroptical spectra of large polypeptides.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana, USA.
authors.forename: K V Jovan
authors.initials: KV
authors.lastname: Jose
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana, USA.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavachari
mesh_terms: D000409:Alanine / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013237:Stereoisomerism
chemical_list: D010455:Peptides; C019529:polyalanine; D000409:Alanine
keywords: Raman optical activity; density functional theory; infrared spectroscopy; isotopic labeling; linear scaling methods; vibrational circular dichroism