| Abstract
| - Infrared absorption and vibrational circular dichroism (IR and VCD) spectra of model fragments of TrpZip-style β-hairpin structures are simulated using density functional theory (DFT) methods to estimate the influenceof fragment size, end effects, conformational irregularities, peptide side chains, and solvent. Differentfragmentation schemes, computing the strands and turn segments separately, were tested by varying the sizesof each and their respective overlaps. For suitably overlapping fragments, atomic property tensors were foundto be reliably transferable, as tested by their ability to generate simulated spectra in good agreement withresults from ab initio DFT computations for the entire peptide. This fragment approach significantly reducescomputational times and opens up a wider range of systems that can be studied with a DFT-based approachas compared to previous methods based on uniform repeating sequences. However, vacuum calculations donot adequately represent the frequency dispersion of solvated molecules, and thus, some alternate strategiesfor solvation correction are explored for improving the simulation accuracy. Unlike for regular periodicsecondary structure, the solvent significantly impacts the spectral shapes of hairpins, due to the differentdegrees of hydration of individual amide groups, which can be exposed to or shielded from water due toexternal vs internal hydrogen bonding. This is amplified by the shielding of selected amides from the solventdue to bulky side chains. The peptide plus solvent was structurally modeled with molecular dynamics methods,and then an electrostatic field-based parametrization correction was added to the force field and intensitytensors to compensate for the solvent dipolar field. The effect of the shielding and subsequent reordering ofmodes has a larger impact on VCD than IR band shapes.
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