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Design rules for optimizing quaternary mixed-metal chalcohalides
Physical Review Materials
2025
9
11
Leveraging active learning-enhanced machine-learned interatomic potential for efficient infrared spectra prediction
npj Computational Materials
2025
11
1
Quantum Chemical Exploration of Nitriles in Prebiotic Chemistry and Astrobiology
The Universe hosts countless different chemical environments, such as planets, moons, comets and the interstellar medium. The diverse pressures, temperatures and chemical compositions of these environments make a wide variety of processes possible. Knowledge about the chemical processes that occur in such remote locations is largely limited by what is observable by telescopes or site-specific missions. Gaining a deeper understanding of this chemistry is valuable when testing different hypotheses regarding the history and evolution of our Universe and can be important for informing the design of space missions. In this thesis we computationally evaluate the thermodynamic and kinetic stability of chemical structures that may be relevant to prebiotic chemistry, the chemistry that preceded life, and astrobiology. The thesis describes the use of steered molecular dynamics to study the formation of iminoacetonitrile, a hydrogen cyanide dimer and a proposed prebiotic intermediate. The mechanism of iminoacetonitrile formation is found to be consistent with an established hypothesis. However, the reaction is predicted to proceed over a timescale of several months near room temperature, two orders of magnitude slower than the rate of polymer appearance. Future studies into the reactivity of iminoacetonitrile are proposed to better delineate a comparison between theory and experiments. We investigate the plausibility for a different kind of membrane structure, the azotosome, to form in the frigid hydrocarbon lakes of Titan. Comparisons of the stability of azotosomes relative to the crystal structure of their building block acrylonitrile predict that self-assembly of such membranes is unlikely.
2020
Understanding the Mechanism of PAQR-2 through Modeling and Simulations
PAQR-2 is a transmembrane protein in C. elegans with seven transmembrane helices and a zinc site. As a homolog to the human ADIPOR receptors, which are involved in regulating membrane fluidity and are of importance when studying glucose toxicity in diabetes patients, the mechanism of PAQR-2 holds many undiscovered secrets to understanding membrane fluidity regulation. PAQR-2 has been shown to be vital for survival in cold temperatures and in the presence of high glucose levels. Other fluidity sensitizing proteins have been shown to change conformation in different membrane environments. In this study, molecular dynamics simulations of PAQR-2 were done with the purpose of observing the structural response of PAQR-2 to different membrane environments. Both simulations of only the transmembrane domain and of the full protein were made. In addition, two loss of function mutants (d282n and g533r) were simulated and compared with the wild-type. Furthermore, the IGLR-2 protein that has been shown to be vital for the function of PAQR-2 was simulated and docked with PAQR-2 yeilding a likely structure for the PAQR-2:IGLR-2 complex. Simulations of PAQR-2 in a thick and ordered DPPE membrane revealed an adaptation of the membrane thickness to accommodate PAQR-2, rather than a structural change within the protein itself. The g533r mutation introduced novel interaction sites between the helices. The d282n mutation resulted in a loss of hydrogen bonds of the residue, which sits close to the zinc site. Protein-protein docking and PMF calculations using umbrella sampling revealed four possible PAQR-2:IGLR-2 complexes. The interactions of the highest scoring complex were analyzed and classified as being primarily weak interactions. The full protein model of PAQR-2 which includes both the transmembrane domain and the cytosolic domain, shows most promise as a model of PAQR-2, as it captures dynamics surrounding the zinc site predicted by the homolog model. Moreover, the full protein model describes different behaviour between wild-type and the d282n mutant not found in the model of only the transmembrane domain. Further optimization of the full protein is required as an un-physical loss of secondary structure occurs in the cytosolic domain when simulated close to the membrane.
2017
Interspecies plasmid transfer appears rare in sequential infections with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae
Diagnostic Microbiology and Infectious Disease
2019
93
4
380-385
The Beginning of HCN Polymerization: Iminoacetonitrile Formation and Its Implications in Astrochemical Environments
ACS Earth and Space Chemistry
2021
5
8
2152-2159
Crossroads at the Origin of Prebiotic Chemical Complexity: Hydrogen Cyanide Product Diversification
The Journal of Physical Chemistry A
2023
127
20
4503-4510
Data‐Driven Compound Identification in Atmospheric Mass Spectrometry
Advanced Science
2023
11
8
A Thermodynamic Landscape of Hydrogen Cyanide-Derived Molecules and Polymers
ACS Earth and Space Chemistry
2024
8
6
1272-1280