Development of a scaled quantum mechanical force field for peptides in aqueous solution

Infrared and Raman vibrational spectroscopies have been useful tools for the study of biomolecules. However, only by normal mode analysis can detailed structural information be obtained from these techniques. Normal mode analysis circulates a vibrational spectrum for comparison with experimental data. The calculation requires an accurate set of force constants, which describe the forces between the atoms in the molecule. Empirical methods were the only means of determining force constants until recently, when the scaled quantum mechanical force field (SQMFF) method was developed (Fogarasi and Pulay, 1985). The SQMFF method determines scale factors to correct ab initio force constants by fitting calculated frequencies to experimentally measured spectra. These corrections are necessary because ab initio force constants contain systematic errors due to assumptions and simplifications made in solving Schrodinger's equation. The scale factors are useful because they are transferable between molecules (Fogarasi and Pulay, 1985; Williams and Lowrey, 1991).;I have built a set of solution phase scale factors and force constants starting from small molecules and moving up in complexity to the alanyl-alanine peptide (Weir et. al., 1996). Different hydrogen bonded structures were included to model the intramolecular hydrogen bonding patterns observed in protein secondary structures. The solution phase scale factors demonstrate good transferability. They provide the basis for calculating vibrational spectra of larger molecules and for understanding the accuracy that can be expected from those calculations. The set of force constants I developed predict the amide I and III frequencies with an average error of 8 cm;Along with the development of the scale factors, vibrational modes were assigned to all observed frequencies for every structure. The assignments and scale factors are internally consistent, making this the most systematic and comprehensive set of vibrational assignments to date, including the first complete assignment of vibrational modes for alanyl-alanine. Reference to this set of assignments will simplify the development of improved force fields.