Importance of Polarization and Charge Transfer Effects to Model the Infrared Spectra of Peptides in Solution

J Chem Theory Comput. 2011 Jun 14;7(6):1840-9. doi: 10.1021/ct2000588. Epub 2011 Apr 29.

Abstract

We present a study of the infrared spectrum of N-methyl acetamide (NMA) performed by using molecular dynamics (MD) with a quantum electronic Hamiltonian. A recently developed method, based on the Born-Oppenheimer approximation and on a semiempirical level of quantum chemistry (SEBOMD), is employed. We focus on the solvent effect on the infrared spectrum of the solute, on its geometry, and on its electrostatic properties. We thus run simulations of NMA in the gas phase and in water (64 solvent molecules with periodic boundary conditions), taking into account its two different conformers-cis and trans. The use of a semiempirical electronic Hamiltonian allows us to explore much larger time scales compared to density functional theory based MD for systems of similar size. NMA represents a simple model system for peptide bonds: those infrared bands that are more significant as a signature of the peptide bond (amide I, II, and III and the N-H stretch) are identified, and the solvent shift is evaluated and compared to experiments. We find a satisfying agreement between our model and experimental measurements, not only for the solvent shift but also for the structural and electrostatic properties of the solute. On the other hand, when a molecular mechanics, nonpolarizable force field is used to run MD, very little or nil solvent effect is observed. By analyzing our results, we propose an explanation of this discrepancy by stressing the importance of mutual polarization and charge transfer in an accurate modeling of the solute-solvent interactions.