Robert W. Newberry 

Robert W. Newberry

Degree Program: Chemistry
Faculty Supervisor: Ronald T. Raines
Phone: (713) 898-0307


Current Research

The primary sequence of a peptide chain controls the structure that the peptide adopts and directs how the chain folds into that structure. The space occupied by bonded atoms in the polypeptide restricts the conformational space available to protein structures, and within this available space, hydrogen bonding, the hydrophobic effect, and electrostatic interactions bias the complex conformational equilibrium of the protein toward particular structures. Recently, a new contribution to protein structure has been identified, termed the n→π* interaction. Particular peptide backbone geometries allow overlap of the p-type lone pair (n) of a carbonyl oxygen with the π* orbital of the carbonyl group on an adjacent residue (Figure 1); the electron delocalization achieved by this orbital overlap is stabilizing and likely further biases the folding of the peptide chain. These n→π* interactions have been implicated in several elements of secondary structure, including α-helices, PPII helices, and β-turns. We now seek to exploit the n→π* interaction to modulate the stability of each of these secondary structures, with the eventual goal of increasing the stability of native proteins and improving the rational encoding of secondary structure into primary amino acid sequences. We are currently investigating the effect of backbone thioamide incorporation on the stability of PPII helices, as previous results have indicated that the thioamide should increase the strength of n→π* donation relative to the amide. We will also study the contribution of n→π* interactions to protein folding kinetics and mechanisms; as the n→π* interaction is both intimate and highly local, we expect it to play a significant role in the early organization of secondary structure. Finally, we aim to identify additional roles of n→π* interactions, with particular focus on protein-ligand interactions, mechanisms of enzymatic catalysis, the structure of organic polymers, and the reactivity of small molecules.


Ragain CM, Newberry RW, Ritchie AW, Webb LJ. The role of electrostatics in differential binding of ralGDS to rap mutations E30D and K31E investigated by vibrational spectroscopy of thiocyanate probes. J Phys Chem B. 2012.

Umali AP, LeBoeuf SE, Newberry RW, Kim S, Tran L, Rome WA, Tian T, Taing D, Hong J, Kwan M, Heymann H, Anslyn EV. Discrimination of flavonoids and red wine varietals by arrays of differential peptidic sensors Chem Sci 2011, 2, 439-445.

Abstract (PDF)

Resume (PDF)





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