This talk will focus on the role of quantum chemical calculations in understanding the fundamentals of peptide catalyst design. This work is done in collaboration with two synthesis groups led by Michel Gagne and Marcey Waters at the University of North Carolina, Chapel Hill. Currently, we are studying the effect of the peptide's dipole moment on transition state energies. Specifically, we are computationally examining the 9-residue-1-histadine alpha helical peptide in catalyzing ester hydrolysis and then compare that to the experimental data. Minima, transition state, and intrinsic reaction coordinate (IRC) calculations are done with Gaussian09 at M06-2X/6-31G(d) in 2,2,2-trifluoroethanol using SMD solvation model, and relative Gibbs Free energies are reported. Conformational search are also done to determine all the possible conformations of the peptide helix as a minimum and its transition state structures when adding to ester. Preliminary computational data show that the peptide helix displays a clear dipole moment along its principal axis, with one positive end and one negative end. The energy barriers are affected simply by the orientation of the charge-separated transition state structure with respect to the peptide. Throughout this project, we will integrate computational and experimental study to find good peptide catalysts for ester hydrolysis as well as to determine how quantum chemical calculations can help create biased high-throughput peptide libraries. Not limited to the described peptide system above, we will also vary the residues around the histidine in order to examine the effect of additional hydrogen bonding or hydrophobic interaction.

Computational study on the effect of dipole moment of alpha-helical peptide as catalysts for ester hydrolysis

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.