The Redinbo Laboratory uses the tools of structural, molecular and chemical biology to examine a range of dynamic cellular processes central to human health. Current projects include the discovery of new antimicrobials targeted to drug-resistant bacteria, the design of novel proteins engineered to detect and eliminate toxic chemicals, and the development of small-molecule to cell-based methods to improve anticancer chemotherapeutics. In addition, we continue to focus on determining the crystal structures of macromolecular complexes, including those involving human nuclear receptors central to transcriptional regulation, bacterial proteins involved in DNA manipulation and human cell contact, and enzymes central to key cellular processes.
The Baer Group currently focuses on two projects, TPEPICO and Aerosol Laser mass spectrometry. TPEPICO, or Threshold PhotoElectron PhotoIon COincidence spectrometry, involves the photoionization of individual molecules coupled with a time of flight (TOF) mass spectrometer to monitor the dissociation of a given molecule as a function of photon energy. Information that can be obtained using this technique includes neutral, radicle, and ion heats of formation and rate information of the dissociation.
The Aerosol lab is studying the coating of oleic acids on both polar and non-polar surfaces to determine the reactivity and how readily coated aerosols form condensed cloud nuclei. Oleic acid is a monounsaturated fatty acid found in cooking oils, meat, and is very abundant in olive oil, thus oleic acid is released during several types of cooking. Oleic acid's double bond is readily attacked by ozone, so this reaction is extremely important to environmental chemistry. Oleic acid can also serve as a model for larger lipid systems and give an insight to the reaction of more complex lipids with ozone.
Researchers in the Berkowitz Group performed molecular dynamics simulations on systems containing phosphatidycholine headgroups attached to graphene plates (PC−headgroup plates) immersed in water to study the interaction between phosphatidylcholine bilayers in water. The potential of mean force (PMF) between PC−headgroup plates shows that the interaction is repulsive.
As described in The Journal of Physical Chemistry B, the investigators observed three distinct regimes in the PMF depending on the interplate distances: the small distance regime, intermediate distance regime, and large distance regime. The researchers believe that the repulsive interaction in the intermediate interplate distance regime is associated with the hydration force due to the removal of water molecules adjacent to the headgroups.
The Baer Group has published a threshold photoelectron photoion coincidence study in which the energy required to dissociatively ionize propene (C3H6 + hv → C3H5+ + H + e-) was measured to be 11.898 ± 0.024 eV. When this is combined with a recently reported ionization energy of the allyl radical, see Figure below, a high precision propene C-H bond energy (BE) as well as the proton affinity (PA) of allene could be established.
This study was complicated by the slow dissociation of the propene ion, which caused previous investigations to be too high, thereby underestimating the PA and overestimating the BE. The Baer group established the correct dissociation onset by measuring the dissociation rate constants as a function of the ion energy by time of flight mass spectrometry, and extrapolating the rate to the dissociation onset.
Carolina Chemist and John P. Barker Distinguished Professor Michael Rubinstein, has been awarded the 2010 Polymer Physics Prize from the American Physical Society. The prize recognizes outstanding contributions in polymer physics research, specifically professor Rubinstein's leadership in the field of structure and dynamics of polymer liquids, interfaces and gels.
Most of the materials around us, from plastics to tires, and inside us, DNA and proteins, are made of polymers - giant, chain-like molecules. The goal of Rubinstein’s research group is to understand how polymers move through a tangle formed by their molecule neighbors and how they are deformed if attached to each other in a network, then pulled apart, like stretching a rubber band. UNC researchers are modeling polymers in the lungs with the goal of developing treatments for diseases such as cystic fibrosis.
The unique properties of polymers that make them the materials of choice in many industries are their enormous size in comparison to ordinary molecules and their ability to change under the influence of surrounding molecules, according to Rubinstein.
Rubinstein received his bachelor’s degree from the California Institute of Technology and his master’s and doctorate degrees from Harvard University. He will be presented the award at a meeting of the American Physical Society in March 2010.
As published in JACS, researchers in the Johnson Group have developed a highly diastereoselective synthesis of 2,6-cis-disubstituted tetrahydropyrans (THPs) via Lewis acid-catalyzed formal [4 + 2] cycloaddition of donor−acceptor cyclobutanes and aldehydes. THP products are formed in up to 96% yield and 99:1 diastereoselectivity.
Aromatic, cinnamyl, and aliphatic aldehydes are competent dipolarophiles in this system. This methodology was extended to a [[2 + 2] + 2] cycloaddition of 4-methoxystyrene, dimethyl methylidene malonate, and an aldehyde to furnish THPs directly without prior isolation of the cyclobutane.
Researchers in the Waters Group, as published in JACS, demonstrate how phosphorylated amino acids were incorporated into a designed β-hairpin peptide to study the effect on β-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same β-hairpin system.
It was found that phosporylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function.
Cellular RNA molecules undergo complex folding transitions to form specific, biologically active, three-dimensional structures. A persistent and poorly explained observation is that many RNAs fold very slowly, on timescales requiring minutes or longer. Slow folding ultimately governs the rate at which an RNA can perform its biological function.
In work reported in PNAS, Stefanie Mortimer in the Weeks Lab used time-resolved SHAPE chemistry to show that slow folding at a single nucleotide in the unusual C2'-endo conformation constitutes the rate-determining step for folding a large 50 kDa RNA. Nucleotides in the C2'-endo conformation are relatively rare but are highly overrepresented in functionally critical RNA motifs. This work thus identifies a surprisingly simple, but likely ubiquitous, mechanism for controlling biological processes involving RNA.