Computation of the amide I band of polypeptides and proteins using a partial Hessian approach.

A partial Hessian approximation for the computation of the amide I band of polypeptides and proteins is introduced. This approximation exploits the nature of the amide I band, which is largely localized on the carbonyl groups of the backbone amide residues. For a set of model peptides, harmonic frequencies computed from the Hessian comprising only derivatives of the energy with respect to the displacement of the carbon, oxygen, and nitrogen atoms of the backbone amide groups introduce mean absolute errors of 15 and 10 cm(-1) from the full Hessian values at the Hartree-Fock/STO-3G and density functional theory EDF16-31G(*) levels of theory, respectively. Limiting the partial Hessian to include only derivatives with respect to the displacement of the backbone carbon and oxygen atoms yields corresponding errors of 24 and 22 cm(-1). Both approximations reproduce the full Hessian band profiles well with only a small shift to lower wave number. Computationally, the partial Hessian approximation is used in the solution of the coupled perturbed Hartree-Fock/Kohn-Sham equations and the evaluation of the second derivatives of the electron repulsion integrals. The resulting computational savings are substantial and grow with the size of the polypeptide. At the HF/STO-3G level, the partial Hessian calculation for a polypeptide comprising five tryptophan residues takes approximately 10%-15% of the time for the full Hessian calculation. Using the partial Hessian method, the amide I bands of the constituent secondary structure elements of the protein agitoxin 2 (PDB code 1AGT) are calculated, and the amide I band of the full protein estimated.