Cross-species permissivity: structure of a goat adeno-associated virus and its complex with the human receptor, AAVR

Adeno-associated virus (AAV) is a small ssDNA satellite virus of high interest (in recombinant form) as a safe and effective gene therapy vector. AAV's human cell entry receptor (AAVR) contains Polycystic Kidney Disease (PKD) domains bound by AAV. Seeking understanding of the spectrum of interactions, goat AAVGo.1 is investigated, because its host is the species most distant from human with reciprocal cross-species cell susceptibility. The structure of AAVGo.1, solved by cryo-EM to 2.9 Å resolution, is most similar to AAV5. Through ELISA studies, it is shown that AAVGo.1 binds to human AAVR (huAAVR) more strongly than do AAV2 or AAV5, and that it joins AAV5 in a class that binds exclusively to PKD domain 1 (PKD1), in contrast to other AAVs that interact primarily with PKD2. The AAVGo.1 cryo-EM structure of a complex with a PKD12 fragment of huAAVR at 2.4 Å resolution shows PKD1 bound with minimal change in virus structure, except for disordering of a neighboring surface loop. Only 4 of the 42 capsid protein sequence differences between AAVGo.1 and AAV5 occur at the PKD1 binding interface. These result in only minor conformational changes in AAVR, including a near rigid domain rotation with maximal displacement of the receptor by ~1 Å. A picture emerges of two classes of AAV with completely different modes of binding to the same AAVR receptor, but within each class atomic interactions are mostly conserved. IMPORTANCE Adeno-Associated Virus (AAV) is a small ssDNA satellite parvovirus. As a recombinant vector with a protein shell encapsidating a transgene, recombinant AAV (rAAV) is a leading delivery vehicle for gene therapy with two FDA-approved treatments and 150 clinical trials for 30 diseases. The human entry receptor huAAVR has five PKD domains. To date, all serotypes, except AAV5, have interacted primarily with the second PKD domain, PKD2. Goat is the AAV host most distant from human with cross-species cell infectivity. AAVGo.1 is similar in structure to AAV5, the two forming a class with a distinct mode of receptor-binding. Within the two classes, binding interactions are mostly conserved, giving an indication of the latitude available in modulating delivery vectors.

Vortex chains induced by anisotropic spin-orbit coupling and magnetic field in spin-2 Bose-Einstein condensates

We investigate the anisotropic spin-orbit coupled spin-2 Bose-Einstein condensates with Ioffe-Pritchard magnetic field. With nonzero magnetic field, anisotropic spin-orbit coupling will introduce several vortices and further generate a vortex chain. Inside the vortex chain, vortices connect to each other, forming a line along the axis. The physical nature of the vortex chain can be explained by the particle current and the momentum distribution. The vortex number inside the vortex chain can be influenced via varying the magnetic field. Through adjusting the anisotropy of the spin-orbit coupling, the direction of the vortex chain is changed, and the vortex lattice can be triggered. Moreover, accompanied by the variation of the atomic interactions, the density and the momentum distribution of the vortex chain are affected. The realization and the detection of the vortex chain are compatible with current experimental techniques.

A Systematic Approach for Semiconductor Half-Heusler

The key to designing a half-Heusler begins from the understanding of atomic interactions within the compound. However, this pool of knowledge in half-Heusler compounds is briefly segregated in many papers for specific explanations. The nature of the chemical bonding has been systematically explored for the large transition-metal branch of the half-Heusler family using density-of-states, charge-density, charge transfer, electron-localization-function, and crystal-orbital-Hamilton-population plots. This review aims to simplify the study of a conventional 18-electron configuration half-Heusler by applying rules proposed by renowned scientists to explain concepts such as Zintl-Klemm, hybridization, and valence electron content (VEC). Atomic and molecular orbital diagrams illustrate the electron orbital transitions and provide clarity to the semiconducting behavior (VEC = 18) of half-Heusler. Eighteen-electron half-Heusler usually exhibits good thermoelectric properties owing to favorable electronic structures such as narrow bandgap (<1.1 eV), thermal stability, and robust mechanical properties. The insights derived from this review can be used to design high-performance half-Heusler thermoelectrics.

The Complementarity Principle—One More Step towards Analytical Docking on the Example of Dihydrofolate Reductase Complexes

New approaches to assessing the “enzyme–ligand” complementarity, taking into account hydrogens, have been proposed. The approaches are based on the calculation of three-dimensional maps of the electron density of the receptor–ligand complexes. The action of complementarity factors, first proposed in this article, has been demonstrated on complexes of human dihydrofolate reductase (DHFR) with ligands. We found that high complementarity is ensured by the formation of the most effective intermolecular contacts, which are provided due to predominantly paired atomic–atomic interactions, while interactions of the bifurcate and more disoriented type are minimized. An analytical docking algorithm based on the proposed receptor–ligand complementarity factors is proposed.

INTERCAAT: identifying interface residues between macromolecules

Summary The Interface Contact definition with Adaptable Atom Types (INTERCAAT) was developed to determine the atomic interactions between molecules that form a known three dimensional structure. First, INTERCAAT creates a Voronoi tessellation where each atom acts as a seed. Interactions are defined by atoms that share a hyperplane and whose distance is less than the sum of each atoms’ Van der Waals radii plus the diameter of a solvent molecule. Interacting atoms are then classified and interactions are filtered based on compatibility. INTERCAAT implements an adaptive atom classification method; therefore, it can explore interfaces between a variety macromolecules. Availability and implementation Source code is freely available at: https://gitlab.com/fiserlab.org/intercaat. Supplementary information Supplementary data are available at Bioinformatics online.

Lattice ground states for embedded-atom models in 2D and 3D

The Embedded-Atom Model (EAM) provides a phenomenological description of atomic arrangements in metallic systems. It consists of a configurational energy depending on atomic positions and featuring the interplay of two-body atomic interactions and nonlocal effects due to the corresponding electronic clouds. The purpose of this paper is to mathematically investigate the minimization of the EAM energy among lattices in two and three dimensions. We present a suite of analytical and numerical results under different reference choices for the underlying interaction potentials. In particular, Gaussian, inverse-power, and Lennard-Jones-type interactions are addressed.

Hard-material Adhesion: Which Scales of Roughness Matter?

Background Surface topography strongly modifies adhesion of hard-material contacts, yet roughness of real surfaces typically exists over many length scales, and it is not clear which of these scales has the strongest effect. Objective: This investigation aims to determine which scales of topography have the strongest effect on macroscopic adhesion. Methods Adhesion measurements were performed on technology-relevant diamond coatings of varying roughness using spherical ruby probes that are large enough (0.5-mm-diameter) to sample all length scales of topography. For each material, more than 2000 measurements of pull-off force were performed in order to investigate the magnitude and statistical distribution of adhesion. Using sphere-contact models, the roughness-dependent effective values of work of adhesion were measured, ranging from 0.08 to 7.15 mJ/m2 across the four surfaces. The data was more accurately fit using numerical analysis, where an interaction potential was integrated over the AFM-measured topography of all contacting surfaces. Results These calculations revealed that consideration of nanometer-scale plasticity in the materials was crucial for a good quantitative fit of the measurements, and the presence of such plasticity was confirmed with AFM measurements of the probe after testing. This analysis enabled the extraction of geometry-independent material parameters; the intrinsic work of adhesion between ruby and diamond was determined to be 46.3 mJ/m2. The range of adhesion was 5.6 nm, which is longer than is typically assumed for atomic interactions, but is in agreement with other recent investigations. Finally, the numerical analysis was repeated for the same surfaces but this time with different length-scales of roughness included or filtered out. Conclusions The results demonstrate a critical band of length-scales—between 43 nm and 1.8 µm in lateral size—that has the strongest effect on the total adhesive force for these hard, rough contacts.

Atomic Simulations of U-Mo Under Irradiation: A New Angular Dependent Potential

Uranium-Molybdenum alloy has been a promising option in the production of metallic nuclear fuels, where the introduction of Molybdenum enhances mechanical properties, corrosion resistance, and dimensional stability of fuel components. Meanwhile, few potential options for molecular dynamics simulations of U and its alloys have been reported due to the difficulty in the description of the directional effects within atomic interactions, mainly induced by itinerant f-electron behaviors. In the present study, a new angular dependent potential formalism proposed by the author’s group has been further applied to the description of the U-Mo systems, which has achieved a moderately well reproduction of macroscopic properties such as lattice constants and elastic constants of reference phases. Moreover, the potential has been further improved to more accurately describe the threshold displacement energy surface at intermediate and short atomic distances. Simulations of primary radiation damage in solid solutions of the U-Mo system have also been carried out and an uplift in the residual defect population has been observed when the Mo content decreases to around 5 wt.%, which corroborates the negative role of local Mo depletion in mitigation of irradiation damage and consequent swelling behavior.