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1. Fusion peptide from SARS-2 spike transforms into a wedge inserted in a bilayer leaflet, and thins the opposite leaflet

   Steven R Van Doren, Benjamin Scott ( February 2022 , Biophysical journal)

   Activation of SARS-CoV-2 Spike deploys its fusion peptide to a membrane of the host cell to infect it. NMR in solution demonstrates that this fusion peptide transforms from intrinsic disorder in solution into a wedge-shaped structure inserted in bilayered micelles. According to NOEs and proximity to a nitroxide spin label deep in the membrane mimic, the globular fold of three helices contrasts the open, extended conformations observed in compact prefusion states. In the hydrophobic, narrow end of the wedge, helices 1 and 2 contact the fatty acyl chains of phospholipids. 50 of the resulting paramagnetic NMR relaxation enhancements and 6 lipid-protein NOEs provided ambiguous distances as collective variables (colvars) to bias and guide MD simulations. Simulations in NAMD using the CHARMM36 forcefield included colvars for 130 medium- and long-range NOEs to maintain the equilibrium structure. In the gently NMR-biased simulations, the fusion peptide maintained its insertion of helices 1 and 2 within a single leaflet while helix 3 remained exposed. A cation occasionally visited the anionic side chains in the loop joining helices 2 and 3 or at the N-terminal end of helix 1. The unoccupied leaflet is thinned and distorted opposite the fusion peptide.The thinning could be related tomore »the fusion peptide promoting formation of the hemi-fusion intermediate in the process of viral-cell fusion. Supported by NSF Rapid award 2030473.« less
2. Enhanced host–guest complexation of short chain perfluoroalkyl substances with positively charged β-cyclodextrin derivatives

   https://doi.org/10.1007/s10847-019-00930-w  

   Weiss-Errico, Mary Jo ; O’Shea, Kevin E. ( July 2019 , Journal of Inclusion Phenomena and Macrocyclic Chemistry)

   Short chain perfluoroalkyl substances (PFAS), replacements for long chain legacy PFAS such as perfluorooctanoic acid (PFOA), have similar toxicity, negative health effects, and exceptional persistence as long chain PFAS. β-Cyclodextrin (β-CD) is a powerful host–guest complexing agent for a number of legacy PFAS, suggesting potential β-CD-based remediation processes. We report herein that the addition of charged functional groups at the perimeter of β-CD has a pronounced influence on the strength of the β-CD:PFAS complex. The presence of a positively charged amine functionality on the perimeter of β-CD significantly increases the complexation of legacy and short chain PFAS. We assigned the enhanced complexation to electrostatic attraction between the negatively charged PFAS head group and the positively charged β-CD derivative. In comparison to neutral β-CD, addition of a negative charge to β-CD decreases complexation to PFAS due to electrostatic repulsion between the negatively charged polar head group of PFAS and the negatively charged β-CD. 19F NMR titration experiments illustrate the complexation of short chain PFAS by positive charged β-CDs over neutral β-CD, with increases up to 20 times depending on the PFAS guest. The results give further understanding to the nature of the β-CD:PFAS host–guest complex and the various intermolecular forces thatmore »drive complexation. Positively charged β-CDs appear to be potential complexing agents for remediation of short chain PFAS.« less
3. Pressure Induced Wetting and Dewetting of the Nonpolar Pocket of Deep-Cavity Cavitands in Water

   https://doi.org/10.1021/acs.jpcb.0c02568  

   Tang, Du ; Dwyer, Tobias ; Bukannan, Hussain ; Blackmon, Odella ; Delpo, Courtney ; Barnett, J. Wesley ; Gibb, Bruce C. ; Ashbaugh, Henry S. ( July 2020 , The Journal of Physical Chemistry B)

   Hydrophobic interactions drive the binding of nonpolar ligands to the oily pockets of proteins and supramolecular species in aqueous solution. As such, the wetting of host pockets is expected to play a critical role in determining the thermodynamics of guest binding. Here we use molecular simulations to examine the impact of pressure on the wetting and dewetting of the nonpolar pockets of a series of deep-cavity cavitands in water. The portals to the cavitand pockets are functionalized with both nonpolar (methyl) and polar (hydroxyl) groups oriented pointing either upward or inward toward the pocket. We find wetting of the pocket is favored by the hydroxyl groups and dewetting is favored by the methyl groups. The distribution of waters in the pocket is found to exhibit a two-state-like equilibrium between wet and dry states with a free energy barrier between the two states. Moreover, we demonstrate that the pocket hydration of the cavitands can be collapsed onto a unified adsorption isotherm by assuming the effective pressures within each cavitand pocket differ by a shift pressure that depends on the chemical identity and number of functional groups placed about the portal. These observations support the development of a twostate capillary evaporation modelmore »that accurately describes the equilibrium between states and naturally gives rise to the effective shift pressures observed from simulation. This work demonstrates that the hydration of host pockets can be tuned following simple design rules that in turn are expected to impact the thermodynamics of guest complexation.« less
4. Quantitative Studies on the Interaction between Saposin-like Proteins and Synthetic Lipid Membranes

   https://doi.org/10.3390/mps5010019  

   Sandin, Suzanne I. ; de Alba, Eva ( February 2022 , Methods and Protocols)

   Members of the saposin-fold protein family and related proteins sharing a similar fold (saposin-like proteins; SAPLIP) are peripheral-membrane binding proteins that perform essential cellular functions. Saposins and SAPLIPs are abundant in both plant and animal kingdoms, and peripherally bind to lipid membranes to play important roles in lipid transfer and hydrolysis, defense mechanisms, surfactant stabilization, and cell proliferation. However, quantitative studies on the interaction between proteins and membranes are challenging due to the different nature of the two components in relation to size, structure, chemical composition, and polarity. Using liposomes and the saposin-fold member saposin C (sapC) as model systems, we describe here a method to apply solution NMR and dynamic light scattering to study the interaction between SAPLIPs and synthetic membranes at the quantitative level. Specifically, we prove with NMR that sapC binds reversibly to the synthetic membrane in a pH-controlled manner and show the dynamic nature of its fusogenic properties with dynamic light scattering. The method can be used to infer the optimal pH for membrane binding and to determine an apparent dissociation constant (KDapp) for protein-liposome interaction. We propose that these experiments can be applied to other proteins sharing the saposin fold.
5. Suppressed Phase Separation of Mixed-Halide Perovskites Confined in Endotaxial Matrices

   Xi Wang, Yichuan Ling ( February 2019 , Nature communications)

   The functionality and performance of a semiconductor is determined by its bandgap. Alloying, as for instance in InxGa1-xN, has been a mainstream strategy for tuning the bandgap. Keeping the semiconductor alloys in the miscibility gap (being homogeneous), however, is non-trivial. This challenge is now being extended to halide perovskites – an emerging class of photovoltaic materials. While the bandgap can be conveniently tuned by mixing different halogen ions, as in CsPb(BrxI1-x)3, the so-called mixed-halide perovskites suffer from severe phase separation under illumination. Here, we discover that such phase separation can be highly suppressed by embedding nanocrystals of mixed-halide perovskites in an endotaxial matrix. The tuned bandgap remains remarkably stable under extremely intensive illumination. The agreement between the experiments and a nucleation model suggests that the size of the nanocrystals and the host-guest interfaces are critical for the photo-stability. The stabilized bandgap will be essential for the development of perovskite-based optoelectronics, such as tandem solar cells and full-color LEDs.