Dimeric State Research Articles

Cryo-EM visualization of state transition during non-homologous end-joining (NHEJ).

DNA double-strand breaks (DSBs) are a highly cytotoxic form of DNA damage and the incorrect repair of DSBs is linked to carcinogenesis. The conserved error-prone non-homologous end joining (NHEJ) pathway has a key role in determining the effects of DSB-inducing agents that are used to treat cancer as well as the generation of the diversity in antibodies and T cell receptors. Using single-particle cryo-electron microscopy, we visualized key DNA-protein complexes that are formed by human NHEJ factors. A near-complete NHEJ reaction cycle and a life cycle of DNA-PKcs (catalytic subunit of the DNA-dependent protein kinase) are proposed from the models. The Ku70/80 heterodimer (Ku), DNA-PKcs, XRCC4 and XLF first form a long-range synaptic complex in which the DNA ends are held approximately 115 Å apart. Two DNA end-bound subcomplexes comprising Ku and DNA-PKcs are linked by interactions between the DNA-PKcs subunits and a scaffold comprising LigIV, XRCC4, and XLF. The relative orientation of the DNA-PKcs molecules suggests a mechanism for autophosphorylation in trans, which leads to substantial outward rotation of both Ku and DNA-PKcs to promote DNA double-strand break exposure and DNA-PKcs dissociation. Upon DNA-PKcs dissociation, the long-range synaptic complex transit into the short-range synaptic complex, within which the Ku-bound DNA ends are aligned for processing and ligation by the XLF-anchored scaffold, and a single catalytic domain of LigIV is stably associated with a nick between the two Ku molecules, suggesting that the joining of both strands of a DSB involves both LigIV molecules. In addition, we captured a dimeric state of catalytically inactive DNA-PKcs, which resembles previously determined structures of PIKK family kinases, revealing a model of the full life cycle of DNA-PKcs during NHEJ.

The role of protein-protein interactions in Fluc dimerization stability and function.

Functional ion channel assembly often requires subunit oligomerization. Yet the molecular factors that define the stability of ion channel complexes in membranes remain to be delineated. Here we investigate this question by studying the dynamic dimerization reaction of the model system Fluc to map out the molecular and physical forces driving this reaction in membranes. Fluc is dual-topology homodimer, where dimerization confers the highly specific fluoride permeation pathway. Our previous analysis demonstrated that a sodium titratable mutant of Fluc participates in a two-step equilibrium dimerization reaction in membranes. First, membrane-dependent dimerization drives subunits to assemble and form a non-contact lipid-solvated stable dimer intermediate by burying a membrane defect imposed in the monomer. However, the fluoride conducting state requires the protein subunits to come closer and expel the lipids to form the fluoride permeation pathway. High resolution crystal structures of Fluc show numerous protein-protein interactions across the dimerization interface, suggesting these interactions might be involved in stabilizing the close-contact dimer state. Alternatively, these contacts may not play a major role in the overall dimer stability but may be important for conferring function. Here, we will investigate how disruption of these protein-protein interactions affects dimerization stability, channel activity or both. Site-directed mutagenesis was employed following four strategies of disruption: (1) reduction of van der Waals interactions by leucine-to-alanine substitutions; (2) removal of potential hydrogen bonds by threonine-to-valine substitutions; (3) decrease backbone flexibility by glycine-to-alanine mutations of the GxxxG dimerization motif; (4) and introduction of bulky tryptophan residues at the interface. Using single-molecule photobleaching analysis to investigate dimer stability in membranes combined with single channel bilayer recordings, these results will provide a quantitative characterization of the contribution of protein-protein interactions to Fluc dimer stability and activity.

Lysine Acetylation Changes the Mechanism of Aβ25-35 Peptide Binding and Dimerization in the DMPC Bilayer.

The impact of Lys28 acetylation on Alzheimer's Aβ peptide binding to the lipid bilayer has not been previously studied, either experimentally or computationally. To probe this common post-translational modification, we performed all-atom replica exchange molecular dynamics simulations targeting binding and aggregation of acetylated acAβ25-35 peptide within the DMPC bilayer. Using the unmodified Aβ25-35 studied previously as a reference, our results can be summarized as follows. First, Lys28 acetylation strengthens the Aβ25-35 hydrophobic moment and consequently promotes the helical structure across the peptide extending it into the N-terminus. Second, because Lys28 acetylation disrupts electrostatic contact between Lys28 and lipid phosphate groups, it reduces the binding affinity of acAβ25-35 peptides to the DMPC bilayer. Accordingly, although acetylation preserves the bimodal binding featuring a preferred inserted state and a less probable surface bound state, it decreases the stability of the former. Third, acetylation promotes acAβ25-35 aggregation and eliminates monomers as thermodynamically viable species. More importantly, acAβ25-35 retains as the most thermodynamically stable the inserted dimer with unique head-to-tail helical aggregation interface. However, due to enhanced helix structure, this dimer state becomes less stable and is less likely to propagate into higher order aggregates. Thus, acetylation is predicted to facilitate the formation of low-molecular-weight oligomers. Other post-translational modifications, including phosphorylation and oxidation, reduce helical propensity and have divergent impact on aggregation. Consequently, acetylation, when considered in its totality, has distinct consequences on Aβ25-35 binding and aggregation in the lipid bilayer.

Theoretical study of the spectroscopy and radiative transition probabilities of Si2 from visible to infrared.

High level ab initio calculations on the electronic states of a silicon dimer (Si2) have been carried out by employing a multi-reference configuration interaction plus Davidson correction (MRCI + Q) approach with the aug-cc-pVQZ basis set. The scalar relativistic correction is taken into consideration by the second-order Douglas-Kroll-Hess approximation. In the present work, the transition properties (oscillator strength, Einstein spontaneous emission coefficient and radiative lifetime) of the singlet-singlet, triplet-triplet, and quintet-quintet transitions of Si2 are discussed. We emphasize the triplet-triplet emission bands H3Σ-u-X3Σ-g, K3Σ-u-X3Σ-g and D3Πu-L3Πg which are dominant for 0-11 (18 822 cm-1), 0-0 (30 672 cm-1), and 0-0 (28 881 cm-1) transitions, respectively. In addition, the strong experimentally observed b1Πu-d1Σ+g band around 4184 cm-1 corresponds to the second 1Σ+g-b1Πu combination in the infrared region. The calculated oscillator strengths of the singlet-singlet transitions (f1Πg-e1Σ-u, 21Πg-b1Πu, b1Πu-d1Σ+g and g1Δu-a1Δg) are in the order of 10-3. From a theoretical point of view, the 0-0 sub-band for the f1Πg-e1Σ-u transition, 0-7 for 21Πg-b1Πu, 0-0 for b1Πu-d1Σ+g and the 0-7 vibronic bands for the g1Δu-a1Δg transition may be observed experimentally. It is expected that the present results could provide theoretical support for a deeper understanding of the experimental Si2 spectra providing further applications in astrophysics.

Immunoselective progression of a multi-epitope-based subunit vaccine candidate to convey protection against the parasite Onchocercalupi

Globalization has resulted in an increasing worldwide movement of humans and animals as well as changes in the external environment, temperature, and social interactions, resulting in the accelerated emergence of new diseases in humans and dogs, such as Onchocerca lupi-caused ocular onchocerciasis. Presently, zoonotic onchocerciasis affects 15.5 million people globally; however, the lack of effective anthelmintics and vaccinations highlighted the disease as a global public health concern. Therefore, the current study offers computational methods for anticipating and creating a multi-epitope subunit vaccine targeting Onchocerca lupi by utilizing suitable linkers and adjuvants to combine CTL, HTL, and BCL epitopes. Three different vaccines (V1, V2, and V3) were designed using three distinct adjuvants and then the vaccine constructs antigenicity, solubility, and non-allergenicity were determined. Then, the physicochemical characteristics of the constructed vaccine candidates were analyzed, and also the tertiary structure of the vaccines was anticipated, which was later verified and refined. Molecular docking and molecular dynamics simulation results showed that the V1 vaccine constructs expected affinity and binding free energy for the dimeric state of human Toll-like receptor-4 (hTLR-4) were promising. These results indicate that the suggested vaccine candidate could probably enhance the immune response to Onchocerca lupi infection. The results should be confirmed in experimental studies.

On a mechanistic impact of transmembrane tetramerization in the pathological activation of RTKs

Constitutive activation of receptor tyrosine kinases (RTKs) via different mutations has a strong impact on the development of severe human disorders, including cancer. Here we propose a putative activation scenario of RTKs, whereby transmembrane (TM) mutations can also promote higher-order oligomerization of the receptors that leads to the subsequent ligand-free activation. We illustrate this scenario using a computational modelling framework comprising sequence-based structure prediction and all-atom 1 µs molecular dynamics (MD) simulations in a lipid membrane for a previously characterised oncogenic TM mutation V536E in platelet-derived growth factor receptor alpha (PDGFRA). We show that in the course of MD simulations the mutant TM tetramer retains stable and compact configuration strengthened by tight protein-protein interactions, while the wild type TM tetramer demonstrates looser packing and a tendency to dissociate. Moreover, the mutation affects the characteristic motions of mutated TM helical segments by introducing additional non-covalent crosslinks in the middle of the TM tetramer, which operate as mechanical hinges. This leads to dynamic decoupling of the C-termini from the rigidified N-terminal parts and facilitates more pronounced possible displacement between the C-termini of the mutant TM helical regions that can provide more freedom for mutual rearrangement of the kinase domains located downstream. Our results for the V536E mutation in the context of PDGFRA TM tetramer allow for the possibility that the effect of oncogenic TM mutations can go beyond alternating the structure and dynamics of TM dimeric states and might also promote the formation of higher-order oligomers directly contributing to ligand-independent signalling effectuated by PDGFRA and other RTKs.

Monomeric and dimeric states of human ZO1-PDZ2 are functional partners of the SARS-CoV-2 E protein

The Envelope (E) protein of SARS-CoV-2 plays a key role in virus maturation, assembly, and virulence mechanisms. The E protein is characterized by the presence of a PDZ-binding motif (PBM) at its C-terminus that allows it to interact with several PDZ-containing proteins in the intracellular environment. One of the main binding partners of the SARS-CoV-2 E protein is the PDZ2 domain of ZO1, a protein with a crucial role in the formation of epithelial and endothelial tight junctions (TJs). In this work, through a combination of analytical ultracentrifugation analysis and equilibrium and kinetic folding experiments, we show that ZO1-PDZ2 domain is able to fold in a monomeric state, an alternative form to the dimeric conformation that is reported to be functional in the cell for TJs assembly. Importantly, surface plasmon resonance (SPR) data indicate that the PDZ2 monomer is fully functional and capable of binding the C-terminal portion of the E protein of SARS-CoV-2, with a measured affinity in the micromolar range. Moreover, we present a detailed computational analysis of the complex between the C-terminal portion of E protein with ZO1-PDZ2, both in its monomeric conformation (computed as a high confidence AlphaFold2 model) and dimeric conformation (obtained from the Protein Data Bank), by using both polarizable and nonpolarizable simulations. Together, our results indicate both the monomeric and dimeric states of PDZ2 to be functional partners of the E protein, with similar binding mechanisms, and provide mechanistic and structural information about a fundamental interaction required for the replication of SARS-CoV-2.

DETERMINATION OF THE MECHANISM OF INTERACTION OF Cu2 +, Pb2 + METHOD OF FTIR SPECTROSCOPY IN THE MIDDLE REGION

The object of the study is to determine the interaction of copper and lead ions in aqueous weakly acidic solutions. According to the analysis of modern scientific works, recently not enough attention is paid to the study of sorption properties of humates after regeneration, so for further use of humic acids as sorbents, including regenerated, it is important to obtain data on stoichiometric interaction of humic acids with various metals. In this work, humic acids were isolated from commercial potassium humate produced in China. Model solutions of copper (II) sulfate and lead (II) acetate were used in the research. The exact content of copper and lead for the final solutions prepared from model with subsequent regeneration of humate-metal complexes was determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Regeneration was carried out by reducing the acidity by adding 1 n nitric acid. The spectra were recorded by FTIR spectroscopy in the middle region. Interpretation of the spectra of the starting humic acids, potassium humates, as well as copper and lead humates was carried out by adjusting the literature data.
 Studies of the structure of humic acids and humates of metals and by this method have shown the active involvement of carboxyl groups in the formation of humate-metal bonds. Humic acids after regeneration (reduction) contain carboxyl groups in the dimerized state, in contrast to freshly prepared humic acids. In lead humates, the above general nature of changes in the spectral pattern from humic acids to lead humates is repeated for copper humates, which can be explained in the general theory of FTIR spectroscopy by increasing the reduced mass of a group of atoms involved in oscillations due to significantly higher atomic mass of pigs. compared to copper.
 It was also found that sorption occurs as a result of stoichiometric reaction, due to which chelate complexes of copper and lead are formed by interaction with oxygen atoms in the carboxyl groups of humate molecules.

Intermolecular Interactions and Charge Resonance Contributions to Triplet and Singlet Exciton States of Oligoacene Aggregates

Intermolecular interactions modulate the electro-optical properties of molecular materials and the nature of low-lying exciton states. Molecular materials composed by oligoacenes are extensively investigated for their semiconducting and optoelectronic properties. Here, we analyze the exciton states derived from time-dependent density functional theory (TDDFT) calculations for two oligoacene model aggregates: naphthalene and anthracene dimers. To unravel the role of inter-molecular interactions, a set of diabatic states is selected, chosen to coincide with local (LE) and charge-transfer (CT) excitations within a restricted orbital space including two occupied and two unoccupied orbitals for each molecular monomer. We study energy profiles and disentangle inter-state couplings to disclose the (CT) character of singlet and triplet exciton states and assess the influence of inter-molecular orientation by displacing one molecule with respect to the other along the longitudinal translation coordinate. The analysis shows that (CT) contributions are relevant, although comparably less effective for triplet excitons, and induce a non-negligible mixed character to the low-lying exciton states for eclipsed monomers and for small translational displacements. Such (CT) contributions govern the La/Lb state inversion occurring for the low-lying singlet exciton states of naphthalene dimer and contribute to the switch from H- to J-aggregate type of the strongly allowed Bb transition of both oligoacene aggregates.

The protein dynamics of bovine and caprine β-lactoglobulin differ as a function of pH

The properties of milk proteins differ between mammalian species. β-Lactoglobulin (βlg) proteins from caprine and bovine milk are sequentially and structurally highly similar, yet their physicochemical properties differ, particularly in response to pH. To resolve this conundrum, we compared the dynamics of both the monomeric and dimeric states for each homologue at pH 6.9 and 7.5 using hydrogen/deuterium exchange experiments. At pH 7.5, the rate of exchange is similar across both homologues, but at pH 6.9 the dimeric states of the bovine βlg B variant homologue have significantly more conformational flexibility compared with caprine βlg. Molecular dynamics simulations provide a mechanistic rationale for the experimental observations, revealing that variant-specific substitutions encode different conformational ensembles with different dynamic properties consistent with the hydrogen/deuterium exchange experiments. Understanding the dynamic differences across βlg homologues is essential to understand the different responses of these milks to processing, human digestion, and differences in immunogenicity.

Relativistic ab initio study on the spectroscopic and radiative properties of the lowest states and modeling of the optical cycles for the LiFr molecule

The LiFr diatomic represents a promising candidate for indirect laser cooling that has not yet been investigated not theoretically or experimentally. The potential energy curves of the ground and low-lying excited states of the LiFr heteronuclear alkali metal dimer are calculated using the Fock-space relativistic coupled cluster theory for the first time. A number of properties such as the electronic term energies, equilibrium internuclear distances, transition and permanent dipole moments, sequences of vibrational energies, harmonic vibrational frequencies, Franck–Condon factors, and radiative lifetimes (including bound and free transitions) are predicted. The probabilities of the two-step schemes (optical cycles) for the transfer process of the LiFr molecules from high excited vibrational states to the ground vibronic state are also predicted. The data obtained would be useful for laser cooling and spectral experiments with LiFr molecules.

Structural Determinants and Functional Significance of Dimerization for Osmosensing Transporter ProP in Escherichia coli.

Osmosensing transporter ProP forestalls cellular dehydration by detecting environments with high osmotic pressure and mediating the accumulation of organic osmolytes by bacterial cells. It is composed of 12 transmembrane helices with cytoplasmic N- and C-termini. In Escherichia coli, dimers form when the C-terminal domains of ProP molecules form homodimeric, antiparallel, α-helical coiled coils. No dominant negative effect was detected when inactive and active ProP molecules formed heterodimers in vivo. Purification of ProP in detergent dodecylmaltoside yielded monomers, which were functional after reconstitution in proteoliposomes. With other evidence, this suggests that ProP monomers function independently whether in the monomeric or dimeric state. Amino acid replacements that disrupted or reversed the coiled coil did not prevent in vivo dimerization of ProP detected with a bacterial two-hybrid system. Maleimide labeling detected no osmolality-dependent variation in the reactivities of cysteine residues introduced to transmembrane helix (TM) XII. In contrast, coarse-grained molecular dynamic simulations detected deformation of the lipid around TMs III and VI, on the lipid-exposed protein surface opposite to TM XII. This suggests that the dimer interface of ProP includes the surfaces of TMs III and VI, not of TM XII as previously suggested by crosslinking data. Homology modeling suggested that coiled-coil formation and dimerization via such an interface are not mutually exclusive. In previous work, alterations to the C-terminal coiled coil blocked co-localization of ProP with phospholipid cardiolipin at E. coli cell poles. Thus, dimerization may contribute to ProP targeting, adjust its lipid environment, and hence indirectly modify its osmotic stress response.

Димеризация фталоцианина алюминия в органической и водно-органической средах

Aluminum phthalocyanine chloride (AlClPc) is a photoactive macroheterocyclic compound, which, in its monomeric form, is used as a photosensitizer (PS) in photodynamic therapy and diagnostics. In this paper, its physicochemical properties were studied in organic (N, N-dimethylformamide, DMF) and aqua-organic (DMF-aqua) media. It has been shown that the hydrophobic properties of AlClPc prevent its widespread use in various pharmacological compositions due to its tendency to aggregate in aqueous solutions, which leads to the formation of non-fluorescent aggregates and a decrease in its photodynamic activity. The geometry and electronic structure of AlClPc in the monomeric and dimerized (H- and 
 J-aggregates) states were studied using quantum-chemical calculations with the help of the electron density functional theory (DFT) method. Different types of orientation during the dimerization of AlClPc molecules are presented: “back to back”, “head to head”, “head to back”, as well as mixed-oriented types. It has been proven that both in DMF and DMF-aqua media, the preferred orientation is “back to back”, without sacrificing the monomeric geometry of the constituent molecules in the dimer. It is shown that in an aqueous organic solvent the AlClPc molecule is easily hydrated with the formation of a coordination bond between the Al atom of the AlClPc molecule and the O atom of the aqua molecule. The bond length is 2.23 Å, and the hydration energy is 16.84 kcal/mol. Hydration promotes the formation of dimers, in which two aqua molecules play the role of "bridges" between two AlClPc molecules. In such dimer, each aqua molecule has two bonds: one coordination bond between its O atom and the Al atom of one of the AlClPc molecules and one hydrogen bond between its H atom and the N atom of another AlClPc molecule. Based on the calculated data obtained, the AlClPc dimers in the DMF medium were assigned to H-aggregates, and in the DMF-water medium, to J-aggregates, respectively.

Structural basis of the key residue W320 responsible for Hsp90 conformational change

The 90-kDa heat shock protein (Hsp90) is a homodimeric molecular chaperone with ATPase activity, which has become an intensely studied target for the development of drugs for the treatment of cancer, neurodegenerative and infectious diseases. The equilibrium between Hsp90 dimers and oligomers is important for modulating its function. In the absence of ATP, the passive chaperone activity of Hsp90 dimers and oligomers has been shown to stabilize client proteins as a holdase, which enhances substrate binding and prevents irreversible aggregation and precipitation of the substrate proteins. In the presence of ATP and its associated cochaperones, Hsp90 homodimers act as foldases with the binding and hydrolysis of ATP driving conformational changes that mediate client folding. Crystal structures of both wild type and W320A mutant Hsp90αMC (middle/C-terminal domain) have been determined, which displayed a preference for hexameric and dimeric states, respectively. Structural analysis showed that W320 is a key residue for Hsp90 oligomerization by forming intermolecular interactions at the Hsp90 hexameric interface through cation-π interactions with R367. W320A substitution results in the formation of a more open conformation of Hsp90, which has not previously been reported, and the induction of a conformational change in the catalytic loop. The structures provide new insights into the mechanism by which W320 functions as a key switch for conformational changes in Hsp90 self-oligomerization, and binding cochaperones and client proteins. Communicated by Ramaswamy H. Sarma

Alkaline State of the Domain-Swapped Dimer of Human Cytochrome c: A Conformational Switch for Apoptotic Peroxidase Activity.

A 2.08 Å structure of an alkaline conformer of the domain-swapped dimer of K72A human cytochrome c (Cytc) crystallized at pH 9.9 is presented. In the structure, Lys79 is ligated to the heme. All other domain-swapped dimer structures of Cytc have water bound to this coordination site. Part of Ω-loop D (residues 70-85) forms a flexible linker between the subunits in other Cytc domain-swapped dimer structures but instead converts to a helix in the alkaline conformer of the dimer combining with the C-terminal helix to form two 26-residue helices that bracket both sides of the dimer. The alkaline transition of the K72A human dimer monitored at both 625 nm (high spin heme) and 695 nm (Met80 ligation) yields midpoint pH values of 6.6 and 7.6, respectively, showing that the Met80 → Lys79 and high spin to low spin transitions are distinct. The dimer peroxidase activity increases rapidly below pH 7, suggesting that population of the high spin form of the heme is what promotes peroxidase activity. Comparison of the structures of the alkaline dimer and the neutral pH dimer shows that the neutral pH conformer has a better electrostatic surface for binding to a cardiolipin-containing membrane and provides better access for small molecules to the heme iron. Given that the pH of mitochondrial cristae ranges from 6.9 to 7.2, the alkaline transition of the Cytc dimer could provide a conformational switch to tune the peroxidase activity of Cytc that oxygenates cardiolipin in the early stages of apoptosis.

Competing spin-orbital singlet states in the 4d4 honeycomb ruthenate Ag3LiRu2O6

When spin-orbit-entangled $d$-electrons reside on a honeycomb lattice, rich quantum states are anticipated to emerge, as exemplified by the $d^5$ Kitaev materials. Distinct yet equally intriguing physics may be realized with a $d$-electron count other than $d^5$. We found that the layered ruthenate Ag$_3$LiRu$_2$O$_6$ with $d^4$ Ru$^{4+}$ ions at ambient pressure forms a honeycomb lattice of spin-orbit-entangled singlets, which is a playground for frustrated excitonic magnetism. Under pressure, the singlet state does not develop the expected excitonic magnetism but experiences two successive transitions to other nonmagnetic phases, first to an intermediate phase with moderate distortion of honeycomb lattice, and eventually to a high-pressure phase with very short Ru-Ru dimer bonds. While the strong dimerization in the high-pressure phase originates from a molecular orbital formation as in the sister compound Li$_2$RuO$_3$, the intermediate phase represents a spin-orbit-coupled $J$-dimer state which is stabilized by the admixture of upper-lying $J_{\rm eff} = 1$-derived states. We argue that the $J$-dimer state is induced by a pseudo-Jahn-Teller effect associated with the low-lying spin-orbital excited states and is unique to spin-orbit-entangled $d^4$ systems. The discovery of competing singlet phases demonstrates rich spin-orbital physics of $d^4$ honeycomb compounds and paves the way for realization of unconventional magnetism.

Unravelling the electronic structure of the silicon dimer using threshold photoelectron spectroscopy

The low-lying electronic states of silicon dimer (Si) and its cation (Si) have been studied by single-photon photoelectron spectroscopy combining a flow-tube reactor, vacuum-ultraviolet synchrotron radiation, and a double imaging photoelectron/photoion spectrometer. The energy range covered in this study (7.0−9.5 eV) allowed to observe several photoionising transitions involving the three lowest electronic states of Si (, , ) and five of the six lowest states of Si (, , , , and ). Using ab initio calculations and Franck-Condon simulations, several electronic transitions are identified which bring new elements in the description of the dense electronic landscapes of the silicon dimer and its cation. Interestingly, one of the most intense transitions is spin-forbidden () and is most probably observed through autoionisation processes by spin interactions.

Dimer states of Rydberg atoms on the Kagome lattice as resources for universal measurement-based quantum computation

We show that the quantum dimer state on the Kagome lattice, which was recently realized with high fidelity in a Rydberg quantum simulator [G. Semeghini et al., Science 374, 6572 (2021)], offers a sufficient resource for universal measurement-based quantum computations. In particular, we provide an efficient encoding of logical qubits in this state and give explicit measurement sequences that implement a universal set of gates on these qubits. Since the building blocks of the proposed measurements have already been experimentally implemented, our work highlights one possible path toward promoting Rydberg simulators to universal quantum computers relying on the measurement-based model of quantum computation with currently existing technology.

Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.

Oligomerization endows proteins with some key properties such as extra-stabilization, long-range allosteric regulation(s), and partnerships not accessible to their monomeric counterparts. How oligomerization is achieved and preserved during evolution is a subject of remarkable scientific relevance. By exploiting the abilities of the machine-learning algorithms implemented in AlphaFold (AF) in predicting protein structures, herein, we report a comprehensive analysis of the structural states of functional oligomers of all members of the KCTD protein family. Interestingly, our approach led to the identification of reliable three-dimensional models for the pentameric states of KCNRG, KCTD6, KCTD4, KCTD7, KCTD9, and KCTD14 and possibly for KCTD11 and KCTD21 that are involved in key biological processes and that were previously uncharacterized from a structural point of view. Although for most of these proteins, the CTD domains lack any sequence similarity, they share some important structural features, such as a propeller-like structure with a central cavity delimited by five exposed and regular β-strands. Moreover, the structure of the related proteins KCTD7 and KCTD14, although pentameric, appears to be characterized by a different organization of the CTD region, with the five chains forming a circle-like structure with a large cavity. Our predictions also suggest that other members of the family, such as KCTD10, KCTD13, and TNFAIP1, present a strong propensity to assume dimeric states. Although the structures of the functional oligomers reported herein represent models that require additional validations, they provide a consistent and global view of KCTD protein oligomerization.

Dimers, trimers, tetramers, and other multimers in a multiband Bose-Hubbard model

We study the bound states of $N$ identical bosons that are described by a multiband Bose-Hubbard model with generic hoppings and an attractive onsite interaction. Using a variational approach, we first derive exact integral equations for the dimers, trimers, tetramers, and other multimers, and then apply them to a one-dimensional sawtooth model that features two bands. In particular we reveal the presence of not only the offsite dimer states which consist of two monomers on different sites even in the strong-coupling limit but also the offsite trimer states which consist of either a dimer on one site and a monomer on another site or three monomers on three different sites. Our variational calculations for the ground states of onsite dimers, onsite trimers and offsite trimers benchmark perfectly well with the DMRG simulations. We also present DMRG results for the ground states of onsite tetramers, offsite tetramers, onsite pentamers, offsite pentamers, and for those of other multimers.