Research Overview

Effects of room temperature ionic liquids on biological molecules

Numerous studies have shown the great potential of ionic liquids to control and manipulate biological systems. Despite the great interest ionic liquids have received, they still remain poorly understood. Our efforts are focused on understanding the effects of ionic liquids on protein structure and dynamics. We have considered the effect of ionic liquids on the fast folding miniprotein Trp-cage, proline-containing dipeptides, and the intrinsically disordered protein FlgM. Our study of Trp-cage revealed similarities between aqueous and ionic liquid environments as well as important differences. Perhaps the most interesting difference between these solvent environments is that the ionic liquid is found to facilitate isomerization of the protein backbone in the vicinity of proline residues. This led us to study isomerization of proline dipeptides in ionic liquids, which showed that ring stacking and solvent hydrogen bonding can promote the cis state over the trans. We are now looking at other fast folding proteins and other important peptides to further characterize ionic liquid effects on proteins.

Relevant publications:

  1. Influence of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage, Journal of Molecular Graphics and Modelling, 62, 202 (2015).
  2. Influence of an Ionic Liquid on the Conformational Sampling of Xaa-Pro Dipeptides, Journal of Molecular Liquids, 227, 66 (2017).
  3. The Ionic Liquid [C4mpy][Tf2N] Induces Bound-like Structure in the Intrinsically Disordered Protein FlgM, Physical Chemistry Chemical Physics, 21, 17950 (2019).
  4. Investigations into the Scope, Efficacy and Antimicrobial Mechanism of the Broad-Spectrum Antiseptic Choline Geranate, PLOS One, 14(9): e0222211 (2019).

Structure and dynamics in electrolytes

Fuel cells consist of an anode and cathode, separated by an electrolyte. Fuel is fed to the cell and directly converted from chemical energy into electricity. Polymer electrolyte membrane fuel cells are a candidate as a clean alternative to combustion engines. Two types of polymer electrolyte membranes used in fuel cells are proton exchange membranes and anion exchange membranes. The general principles are similar, but in a proton exchange membrane fuel cell H+ is generated at the anode and conducted through the membrane to the cathode, while in an anion exchange membrane fuel cell HO- is generated at the cathode and conducted through the membrane to the anode. In each case an effective membrane facilitates the transport of the charge carrier and associated water molecules to the opposite electrode, but minimizes the flow of unreacted fuel, oxygen gas, and electrons, while efficiently dissipating heat. There are a number of performance issues that continue to limit the viability of polymer electrolyte membrane fuel cells, including material durability, hydration management, crossover of unreacted fuel, and material morphological effects. To help meet these challenges we are studying the transport of ions in membranes, and specifically correlating ion transport with material composition, the transport and distribution of water in the membranes, exotic membrane materials and their potential effect on the desired performance of fuel cells, and the role of large-scale morphology on molecular-scale properties.

Relevant publications:

  1. Hydroxide Solvation and Transport in Anion Exchange Membranes, Journal of the American Chemical Society, 138, 991 (2016).
  2. Development of a PEO-based lithium ion conductive epoxy resin polymer electrolyte, Solid State Ionics, 326, 150 (2018).
  3. Structure and diffusion of molten alkali carbonate salts at the liquid-vacuum interface, PeerJ Physical Chemistry, 1:e3 (2019).

Past projects

Physical behavior of non-biological nucleic acids

The pathway from prebiotic chemistry to modern biology has proven difficult to resolve because the prebiotic chemical reactions leading to the modern DNA-protein machinery are currently unknown. A primitive polymer that could spontaneously form from available precursors may have preceded DNA as the first genetic material. The discovery of molecules similar to nucleotides and amino acids as components of meteorites has reinvigorated interest this area of research, sampling of source material at extraterrestrial locations is possible and it is essential to define plausible DNA and protein precursors to target for detection through remote sensing. 5-hydroxymethylated pyrimidines (HMPs) have been identified as potential nucleotide precursors based on research that has shown the HMPs can spontaneously form oligomers up to eight monomers in length in aqueous solutions and these oligomers contain uracil and cytosine. However, no research has been done to examine the thermodynamic and dynamic properties of the HMP monomers or oligomers they form. Using molecular dynamics simulations we have identified differences in the intermolecular interactions of monomer and oligomer systems of HMPs, which may have an effect on the ability of oligomers to form secondary structure. We show that stacking interactions of HMPs may be a strong driving force for aggregation of both monomers and small oligomers, which may be fundamentally important towards the synthesis of larger oligomeric and polymeric structures.

Influence of Environment and Temperature on the Structure of the Thermophilic Intrinsically Disordered Protein FlgM

Thermophilic organisms have evolved to perform almost identical biological mechanisms as their mesophilic counterparts to sustain life while maintaining a high level of stability and efficiency, even at high temperatures. There have been several MD studies to determine which structural characteristics contribute to thermophilicity in a variety of proteins. These factors include stable salt bridges, hydrogen bonds, compact structure, and overall flexibility, among others. The balance of these factors varies greatly from protein to protein. At the same time, intrinsically disordered proteins (IDPs) have evolved to eschew traditional protein order to function more efficiently while exhibiting less secondary and tertiary protein structure. FlgM, or flagellar anti-sigma factor, is one such IDP that also has both mesophilic and thermophilic homologues. This project focuses on the relationship between specific structural characteristics of FlgM in thermophilic Aquifex aeolicus that contribute to the stability of the ordered and disordered states as well as the shift that occurs between the two when the temperature is altered.

Water in heterogeneous environments

Water plays an important role in numerous chemical and physical processes. Despite the ubiquitous importance of water, there remain unresolved aspects of its behavior. We are interested in understanding how the observable properties of water in the condensed phase arise from molecular-scale interactions.

On earth, water commonly occurs in gaseous, liquid, and solid phases, but other phases of water are found to form at extreme temperatures and pressures. Even at temperatures and pressures commonly observed on earth, pure water can exist in more complex forms like amorphous ice. The complexity is compounded when certain solutes are present in water, for example when methane is present at slightly elevated pressures methane clathrate forms. The balance between phases is relevant for our understanding of nature and the development of new technologies. We are developing and applying methods to efficiently determine the relative stability of different phases of water.

Relevant publications: Propensity of Hydrated Excess Protons and Hydroxide Anions for the Air-Water Interface, Journal of the American Chemical Society, 137, 12610 (2015).

Gas dynamics in nanoporous materials

We are motivated by remaining challenges facing emerging clean energy technologies. Chemically storing energy in small molecules like hydrogen or methane offers long term stability and ready conversion to usable energy. But the use of these fuels is hampered by their storage density and safety. To achieve high energies densities for natural gas, it is currently commonly stored as compressed natural gas (high pressures) or low temperatures (liquified natural gas), but the pressures or temperatures required can be expensive and unsafe to maintain. Therefore there is an active search underway for materials that readily take-up and release gases at moderate temperatures and pressures. One such class of materials are metal-organic frameworks, commonly called MOFs. MOFs are compounds comprised of metal ions connected in an extended network by organic ligands. In addition to gas storage, MOFs have shown promise for many other applications, including gas separations and catalysis. We are interested in understanding how gas binding and transport depend on material characteristics.