Samuel Krimm

Our research program has two main goals: developing infrared and Raman spectroscopy as a rigorous technique for studying the three-dimensional structures of peptides and proteins, and developing physically reliable potential energy functions for studying the conformation and molecular dynamics of biomacromolecules.

The vibrational spectroscopic studies involve experimental determination of infrared and Raman spectra combined with normal mode calculations of expected vibrational frequencies. Our goal is to provide rigorous predictions of the spectra to be associated with any given structure. Since the reliability of a normal mode calculation is determined by the validity of the force field, we have devoted significant effort to developing such force fields. Our early work concentrated on empirically refined peptide force fields, and these have proven quite successful in analyzing the vibrational spectra of peptides, polypeptides and proteins. We now rely on quantum mechanically derived force fields.

In an effort to develop conformation-dependent force fields, we have turned to the refinement of better molecular mechanics energy functions. We have found a method for converting spectroscopic force fields analytically into molecular mechanics energy functions. In this approach we use ab initio structures, energies, and scaled force fields, and since this treatment preserves spectroscopic accuracy we call these spectroscopically determined force fields (SDFF). This research involves ab initio computations, spectroscopic assignments, and development of optimum molecular mechanics functional forms. For the latter, we give special attention to detailed characterization of the electrostatics, including polarizability and conformational dependence of charges, to a proper physical description of hydrogen bonding, and to subtle structural properties of the peptide group.

We work on peptides, polypeptides, and proteins. Problems are chosen for their inherent biological relevance as well as for how they can elucidate and advance the use of the techniques.

Research Areas(s)

• Vibrational Spectroscopic and Energy Function Studies of Protein Structure