Ivermectin affects Arabidopsis thaliana microtubules through predicted binding site of β-tubulin.

The ivermectin is a potent nematocide and insecticide, which has low toxicity for humans and domestic animals, but due to low biotransformation, it can be dangerous for non-target organisms. The recent determination of ivermectin absorption and accumulation in tissues of higher plants and multiple shreds of evidence of its negative impact on plant physiology provide a basis for the search for ivermectin's molecular targets and mechanisms of action in plant cells. In this research, for the first time, the ivermectin effect on microtubules of Arabidopsis thaliana cells was studied.

Spectral Response of Disorder-Free Localized Lattice Gauge Theories.

We show that certain lattice gauge theories exhibiting disorder-free localization have a characteristic response in spatially averaged spectral functions: a few sharp peaks combined with vanishing response in the zero frequency limit. This reflects the discrete spectra of small clusters of kinetically active regions formed in such gauge theories when they fragment into spatially finite clusters in the localized phase due to the presence of static charges. We obtain the transverse component of the dynamic structure factor, which is probed by neutron scattering experiments, deep in this phase from a combination of analytical estimates and a numerical cluster expansion.

Manipulation of fractionalized charge in the metastable topologically entangled state of a doped Wigner crystal.

Metastability of many-body quantum states is rare and still poorly understood. An exceptional example is the low-temperature metallic state of the layered dichalcogenide 1T-TaS in which electronic order is frozen after external excitation. Here we visualize the microscopic dynamics of injected charges in the metastable state using a multiple-tip scanning tunnelling microscope.

Integrated workflow for the identification of new GABA R positive allosteric modulators based on the in silico screening with further in vitro validation. Case study using Enamine's stock chemical space.

Numerous studies reported an association between GABA R subunit genes and epilepsy, eating disorders, autism spectrum disorders, neurodevelopmental disorders, and bipolar disorders. This study was aimed to find some potential positive allosteric modulators and was performed by combining the in silico approach with further in vitro evaluation of its real activity. We started from the GABA R-diazepam complexes and assembled a lipid embedded protein ensemble to refine it via molecular dynamics (MD) simulation.

In silico induced effect of N-ε-lysine acetylation on microtubule stability and subsequent interaction of microtubule-associated proteins.

Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals.

Light-Induced Quantum Droplet Phases of Lattice Bosons in Multimode Cavities.

Multimode optical cavities can be used to implement interatomic interactions which are highly tunable in strength and range. For bosonic atoms trapped in an optical lattice we show that, for any finite range of the cavity-mediated interaction, quantum self-bound droplets dominate the ground state phase diagram. Their size and in turn density is not externally fixed but rather emerges from the competition between local repulsion and finite-range cavity-mediated attraction.

Anti-MRSA drug discovery by ligand-based virtual screening and biological evaluation.

S. aureus resistant to methicillin (MRSA) is one of the most-concerned multidrug resistant bacteria, due to its role in life-threatening infections. There is an urgent need to develop new antibiotics against MRSA.

CATMoS: Collaborative Acute Toxicity Modeling Suite.

Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests.

Disorder-Free Localization in an Interacting 2D Lattice Gauge Theory.

Disorder-free localization has been recently introduced as a mechanism for ergodicity breaking in low-dimensional homogeneous lattice gauge theories caused by local constraints imposed by gauge invariance. We show that also genuinely interacting systems in two spatial dimensions can become nonergodic as a consequence of this mechanism. This result is all the more surprising since the conventional many-body localization is conjectured to be unstable in two dimensions; hence the gauge invariance represents an alternative robust localization mechanism surviving in higher dimensions in the presence of interactions.

Transformer-CNN: Swiss knife for QSAR modeling and interpretation.

We present SMILES-embeddings derived from the internal encoder state of a Transformer [1] model trained to canonize SMILES as a Seq2Seq problem. Using a CharNN [2] architecture upon the embeddings results in higher quality interpretable QSAR/QSPR models on diverse benchmark datasets including regression and classification tasks. The proposed Transformer-CNN method uses SMILES augmentation for training and inference, and thus the prognosis is based on an internal consensus.

Structure-Activity Relationship Modeling and Experimental Validation of the Imidazolium and Pyridinium Based Ionic Liquids as Potential Antibacterials of MDR and .

Online Chemical Modeling Environment (OCHEM) was used for QSAR analysis of a set of ionic liquids (ILs) tested against multi-drug resistant (MDR) clinical isolate and strains. The predictive accuracy of regression models has coefficient of determination q = 0.66 - 0.

Proposal of Potent Inhibitors for a Bacterial Cell Division Protein FtsZ: Molecular Simulations Based on Molecular Docking and ab Initio Molecular Orbital Calculations.

The inhibition of a bacterial cell division protein, filamentous temperature-sensitive Z (FtsZ), prevents the reproduction of . To propose potent inhibitors of FtsZ, the binding properties of FtsZ with various derivatives of Zantrin ZZ3 were investigated at an electronic level, using molecular simulations. We here employed protein-ligand docking, classical molecular mechanics (MM) optimizations, and ab initio fragment molecular orbital (FMO) calculations.

State-of-the-art augmented NLP transformer models for direct and single-step retrosynthesis.

We investigated the effect of different training scenarios on predicting the (retro)synthesis of chemical compounds using text-like representation of chemical reactions (SMILES) and Natural Language Processing (NLP) neural network Transformer architecture. We showed that data augmentation, which is a powerful method used in image processing, eliminated the effect of data memorization by neural networks and improved their performance for prediction of new sequences. This effect was observed when augmentation was used simultaneously for input and the target data simultaneously.

Focused Library Generator: case of Mdmx inhibitors.

We present a Focused Library Generator that is able to create from scratch new molecules with desired properties. After training the Generator on the ChEMBL database, transfer learning was used to switch the generator to producing new Mdmx inhibitors that are a promising class of anticancer drugs. Lilly medicinal chemistry filters, molecular docking, and a QSAR IC model were used to refine the output of the Generator.

Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection.

Objectives: This study investigated how different concentrations of doxorubicin (DOX) can affect the function of cardiac cells. This study also examined whether activation of prokineticin receptor (PKR)-1 by a nonpeptide agonist, IS20, prevents DOX-induced cardiovascular toxicity in mouse models.

Background: High prevalence of heart failure during and following cancer treatments remains a subject of intense research and therapeutic interest.

Phase transitions and pattern formation in ensembles of phase-amplitude solitons in quasi-one-dimensional electronic systems.

Most common types of symmetry breaking in quasi-one-dimensional electronic systems possess a combined manifold of states degenerate with respect to both the phase θ and the amplitude A sign of the order parameter Aexp(iθ). These degrees of freedom can be controlled or accessed independently via either the spin polarization or the charge densities. To understand statistical properties and the phase diagram in the course of cooling under the controlled parameters, we present here an analytical treatment supported by Monte Carlo simulations for a generic coarse-grained two-field model of XY-Ising type.

A Survey of Multi-task Learning Methods in Chemoinformatics.

Despite the increasing volume of available data, the proportion of experimentally measured data remains small compared to the virtual chemical space of possible chemical structures. Therefore, there is a strong interest in simultaneously predicting different ADMET and biological properties of molecules, which are frequently strongly correlated with one another. Such joint data analyses can increase the accuracy of models by exploiting their common representation and identifying common features between individual properties.

Modeling of networks and globules of charged domain walls observed in pump and pulse induced states.

Experiments on optical and STM injection of carriers in layered MX materials revealed the formation of nanoscale patterns with networks and globules of domain walls. This is thought to be responsible for the metallization transition of the Mott insulator and for stabilization of a "hidden" state. In response, here we present studies of the classical charged lattice gas model emulating the superlattice of polarons ubiquitous to the material of choice 1T - TaS.

Structural and functional features of lysine acetylation of plant and animal tubulins.

The study of the genome and the proteome of different species and representatives of distinct kingdoms, especially detection of proteome via wide-scaled analyses has various challenges and pitfalls. Attempts to combine all available information together and isolate some common features for determination of the pathway and their mechanism of action generally have a highly complicated nature. However, microtubule (MT) monomers are highly conserved protein structures, and microtubules are structurally conserved from Homo sapiens to Arabidopsis thaliana.

MAST-like protein kinase IREH1 from Arabidopsis thaliana co-localizes with the centrosome when expressed in animal cells.

The similarity of IREH1 (Incomplete Root Hair Elongation 1) and animal MAST kinases was confirmed; IREH1cDNA was cloned while expressing in cultured animal cells co-localized with the centrosome. In mammals and fruit flies, microtubule-associated serine/threonine-protein kinases (MAST) are strongly involved in the regulation of the microtubule system. Higher plants also possess protein kinases homologous to MASTs, but their function and interaction with the cytoskeleton remain unclear.

3D-modeling of carboxyl-terminal phosphorylation of plant αβ-tubulin and its role in kinesin-8/microtubule interaction.

The results of computer modeling of plant kinesin-8/αβ-tubulin complexes with such αβ-tubulins' modified amino acid residues as phosphorylated Tyr262 and Tyr107 are reported in this paper. The molecular dynamics of these modified complexes in comparison with the dynamics of non-modified ones suggests that the phosphorylation of both α- and β-tubulins reveals stabilizing effect on the protein structure around the modified residue. It was found also that the phosphorylation of Tyr107 in β-tubulin molecule favors to more advantageous kinesin-8 binding with the phosphorylated microtubule surface in terms of energy.

Protein phosphatases potentially associated with regulation of microtubules, their spatial structure reconstruction and analysis.

According to the sequence and profile comparison with known catalytic domains, where identified protein phosphatases potentially involved in regulation of microtubule dynamics and structure from Arabidopsis thaliana, Nicotiana tabacum, Medicago sativa, Oryza sativa subsp. japonica, Zea mays, and Triticum aestivum. Selected proteins were related to classical non-receptor, serine/threonine-specific and dual protein phosphatases.

3D structure prediction of histone acetyltransferase proteins of the MYST family and their interactome in Arabidopsis thaliana.

Histone lysine acetylation is a reversible post-translational modification that does not involve changes in DNA sequences. Enzymes play an important role in developmental processes and their deregulation has been linked to the progression of diverse disorders. The HAT enzyme family fulfills an important role in various developmental processes mediated by the state of chromatin, and have been attributed to its deregulation.