Energy Functions for Spectroscopy and Dynamics Studies of Proteins

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Accurate potential energy functions for polypeptide chains have two important uses. For spectroscopy, they provide the means to calculate reliable normal mode frequencies of peptides and proteins for fundamental analyses of structure and interactions from infrared and Raman spectra. For molecular mechanics (MM) and dynamics (MD) studies, they provide the physical accuracy needed for reliable predictions of structures, energies, and dynamics of proteins. Current standard functions do not meet such standards since they give spectroscopically poor reproduction of vibrational frequencies. Using a method developed in his laboratory, called a spectroscopically determined force field (SDFF), such deficiencies have been overcome. The goal of this project is to determine and incorporate into an SDFF for the polypeptide chain those components of an MM energy function that will give it the needed accuracy for reliable simulations of proteins. Polarizability will be fully included in the SDFF, based on a recently developed electrostatic model for this property of polar groups. Structural features of the peptide group that depend on pyramidalization at the nitrogen atom will be further elucidated and parameterized. These include the explicit incorporation of charge fluxes, i.e., the dependence of charge on conformation, which are also essential to computing reliable infrared band intensities. Previous studies of typical N-H...O hydrogen bonds will be extended to include C-H...O hydrogen bonds, which have recently been found to be important in protein structures. SDFF descriptions of O-H...O hydrogen bonding in water and alcohols will be developed. The results of this research will have broad scientific and educational impacts. The ability to more reliably calculate structural and energetic, as well as spectroscopic, characteristics of proteins will lead to more accurate predictions of their properties. This will lead to deeper insights into functions of these biologically important molecules. The developments from this research will be disseminated to the scientific community, will result in the advanced training of graduate students and postdocs, and will be reflected in curricular themes in undergraduate courses, thus contributing to the integration of research and education. This project is supported by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Division of Physics in the Mathematical and Physical Sciences Directorate.