Interfacial Enrichment of Lauric Acid Assisted by Long-Chain Fatty Acids, Acidity and Salinity at Sea Spray Aerosol Surfaces.

Surfactant monolayers at sea spray aerosol (SSA) surfaces regulate various atmospheric processes including gas transfer, cloud interactions, and radiative properties. Most experimental studies of SSA employ a simplified surfactant mixture of long-chain fatty acids (LCFAs) as a proxy for the sea surface microlayer or SSA surface. However, medium-chain fatty acids (MCFAs) make up nearly 30% of the FA fraction in nascent SSA. Given that LCFA monolayers are easily disrupted upon the introduction of chemical heterogeneity (such as mixed chain lengths), simple FA proxies are unlikely to represent realistic SSA interfaces. Integrating experimental and computational techniques, we characterize the impact that partially soluble MCFAs have on the properties of atmospherically relevant LCFA mixtures. We explore the extent to which the MCFA lauric acid (LA) is surface stabilized by varying acidity, salinity, and monolayer composition. We also discuss the impacts of pH on LCFA-assisted LA retention, where the presence of LCFAs may shift the surface-adsorption equilibria of laurate─the conjugate base─toward higher surface activities. Molecular dynamic simulations suggest a mechanism for the enhanced surface retention of laurate. We conclude that increased FA heterogeneity at SSA surfaces promotes surface activity of soluble FA species, altering monolayer phase behavior and impacting climate-relevant atmospheric processes

#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol

We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus obscure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized

Beyond Shielding: The Roles of Glycans in the SARS-CoV‑2 Spike Protein

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 28,000,000 infections and 900,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viral fusion proteins, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of the glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the roles of glycans and on the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the "down" state. Additionally, end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of the SARS-CoV-2 S protein, which may be exploited in the therapeutic efforts targeting this molecular machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development

From Viruses to Sea Spray: Applications of All-Atom Molecular Dynamics Simulations to Environmental and Biological Aerosol Systems

Aerosols are solid or liquid particles suspended in the air that can have far-reaching impacts on climate and human health. Aerosols impact climate through their radiative properties and their ability to seed cloud droplets or ice crystals. They also provide surfaces at which heterogeneous multiphase reactions can occur and serve as sinks for atmospheric sulfur, carbon and nitrogen. From a human health perspective, the physical and chemical properties of aerosols including their size, shape, and composition, can impact their transfer and deposition into the lungs. Smaller particles in particular can contain pollutants and pathogens and are able to travel deeper into the bronchioles to trigger irritation and infection. This body of work applies molecular dynamics simulations to understand aerosol systems, investigating their morphologies, impacts on climate, and ultimately their role in transporting the airborne SARS-CoV-2 virus. Molecular simulation and analysis methods are integrated with experiment to first probe surfactant interfaces with varying levels of chemical complexity, then to explore whole aerosol dynamics and phase within the context of understanding impacts of sea spray aerosols (SSA) on climate. This work shows that 1) surfactant charge modulates the surface activity of Burkholderia cepacia lipase at lipid monolayer interfaces; 2) calcium enhances polysaccharide adsorption to fatty acid monolayers; and 3) divalent cations induce morphological changes in LPS-containing aerosols, hindering the reactive uptake of atmospheric nitric acid. This dissertation also describes methods for building large-scale, intact SSA models with full chemical complexity and shows how organic components distribute throughout the aerosol, suggesting that SSA may adopt microemulsion-like morphologies. Finally, a workflow is developed to build ultra-large systems for the study of airborne disease, demonstrating the successful construction and simulation of 1) the SARS-CoV-2 wild type envelope, and 2) a billion-atom respiratory aerosol containing the full breadth of chemical complexity, including the first all-atom model of the Delta SARS-CoV-2 envelope and never-before-modeled pulmonary mucins. The latter project presents the first atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol and represents a novel approach to investigating the infection mechanisms of airborne pathogens

Carotenoid Variation in Roseiflexus castenholzii under Native-Like Growth Conditions

Mentor: Robert E. Blankenship From the Washington University Undergraduate Research Digest: WUURD, Volume 9, Issue 1, Fall 2013. Published by the Office of Undergraduate Research. Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences

Calcium Bridging Drives Polysaccharide Co-Adsorption to a Proxy Sea Surface Microlayer

Saccharides comprise a significant mass fraction of organic carbon in sea spray aerosol (SSA), but the mechanisms through which saccharides are transferred from seawater to the ocean surface and eventually into SSA are unclear. It is hypothesized that saccharides cooperatively adsorb to other insoluble organic matter at the air/sea interface, known as the sea surface microlayer (SSML). Using a combination of surface-sensitive infrared reflection-absorption spectroscopy and all-atom molecular dynamics simulations, we demonstrate that the marine-relevant, anionic polysaccharide alginate co-adsorbs to an insoluble palmitic acid monolayer via divalent cationic bridging interactions. Ca2+ induces the greatest extent of alginate co-adsorption to the monolayer, evidenced by the ~30% increase in surface coverage, whereas Mg2+ only facilitates one-third the extent of co-adsorption at seawater-relevant cation concentrations due to its strong hydration propensity. Na+ cations alone do not facilitate alginate co-adsorption, and palmitic acid protonation hinders the formation of divalent cationic bridges between the palmitate and alginate carboxylate moieties. Alginate co-adsorption is largely confined to the interfacial region beneath the monolayer headgroups, so surface pressure, and thus monolayer surface coverage, only changes the amount of alginate co-adsorption by less than 5%. Our results provide physical and molecular characterization of a potentially significant polysaccharide enrichment mechanism within the SSML

Mesoscale All-Atom Influenza Virus Simulations Suggest New Substrate Binding Mechanism

Influenza virus circulates in human, avian, and swine hosts, causing seasonal epidemic and occasional pandemic outbreaks. Influenza neuraminidase, a viral surface glycoprotein, has two sialic acid binding sites. The catalytic (primary) site, which also binds inhibitors such as oseltamivir carboxylate, is responsible for cleaving the sialic acid linkages that bind viral progeny to the host cell. In contrast, the functional annotation of the secondary site remains unclear. Here, we better characterize these two sites through the development of an all-atom, explicitly solvated, and experimentally based integrative model of the pandemic influenza A H1N1 2009 viral envelope, containing ∼160 million atoms and spanning ∼115 nm in diameter. Molecular dynamics simulations of this crowded subcellular environment, coupled with Markov state model theory, provide a novel framework for studying realistic molecular systems at the mesoscale and allow us to quantify the kinetics of the neuraminidase 150-loop transition between the open and closed states. An analysis of chloride ion occupancy along the neuraminidase surface implies a potential new role for the neuraminidase secondary site, wherein the terminal sialic acid residues of the linkages may bind before transfer to the primary site where enzymatic cleavage occurs. Altogether, our work breaks new ground for molecular simulation in terms of size, complexity, and methodological analyses of the components. It also provides fundamental insights into the understanding of substrate recognition processes for this vital influenza drug target, suggesting a new strategy for the development of anti-influenza therapeutics

Revealing the Impacts of Chemical Complexity on Submicron Sea Spray Aerosol Morphology

Sea spray aerosol (SSA) ejected through bursting bubbles at the ocean surface are complex mixtures of salts and organic species. Composition affects their ability to form marine clouds which cover nearly three-quarters of the Earth and play a critical role in the climate system. Submicron SSA particles have long lifetimes in the atmosphere and impact the Earths climate, yet their cloud-forming potential is difficult to study at the single-particle level using conventional experimental techniques due to their small size. Here, we use large-scale molecular dynamics (MD) simulations as a computational microscope to provide never-before-seen, dynamical views of 40-nm model aerosol particles and their detailed molecular morphologies. We investigate how increasing chemical complexity impacts the distribution and partitioning of organic material throughout individual particles for a range of organic constituents with varying chemical properties. Our simulations show that organic surfactants commonly found in SSA readily partition between both the surface and interior of the aerosol, indicating that nascent SSA may be more heterogeneous than traditional morphological models suggest. We support our computational observations of heterogeneity at the SSA surface with Brewster angle microscopy on model interfaces. Ultimately, our work establishes large-scale MD simulations as a novel technique for interrogating aerosols at the single-particle level, and shows the morphological mechanisms underlying why submicron SSA readily absorb waterand thus have a higher cloud forming potentialthan would otherwise be predicted for organic-rich aerosols