Massive Sampling Strategy for Antibody-Antigen Targets in CAPRI Round 55 With MassiveFold.

Massive sampling with AlphaFold2 improves protein-protein complex predictions. This has been shown during the last CASP15-CAPRI blind prediction round by the AFsample tool. However, more difficult targets including antibody-antigen binding remain challenging.

Antifungal and anti-biofilm effects of hydrazone derivatives on spp.

Worldwide, invasive candidiasis are a burden for the health system due to difficulties to manage patients, to the increasing of the resistance of the current therapeutics and the emergence of naturally resistant species of . In this context, the development of innovative antifungal drugs is urgently needed. During invasive candidiasis, yeast is submitted to many stresses (oxidative, thermic, osmotic) in the human host.

MassiveFold: unveiling AlphaFold's hidden potential with optimized and parallelized massive sampling.

Massive sampling in AlphaFold enables access to increased structural diversity. In combination with its efficient confidence ranking, this unlocks elevated modeling capabilities for monomeric structures and foremost for protein assemblies. However, the approach struggles with GPU cost and data storage.

CAPRI-Q: The CAPRI resource evaluating the quality of predicted structures of protein complexes.

Protein interactions are essential for cellular processes. In recent years there has been significant progress in computational prediction of 3D structures of individual protein chains, with the best-performing algorithms reaching sub-Ångström accuracy. These techniques are now finding their way into the prediction of protein interactions, adding to the existing modeling approaches.

Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment.

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target.

Synthesis and Biological Activity of a New Indenoisoquinoline Copper Derivative as a Topoisomerase I Inhibitor.

Topoisomerases are interesting targets in cancer chemotherapy. Here, we describe the design and synthesis of a novel copper(II) indenoisoquinoline complex, . The new organometallic compound exhibits a cytotoxic effect on five adenocarcinoma cell lines (MCF-7, MDA-MB-231, HeLa, HT-29, and DU-145) with the lowest IC (0.

Epigenomic divergence correlates with sequence polymorphism in Arabidopsis paralogs.

Processes affecting rates of sequence polymorphism are fundamental to the evolution of gene duplicates. The relationship between gene activity and sequence polymorphism can influence the likelihood that functionally redundant gene copies are co-maintained in stable evolutionary equilibria vs other outcomes such as neofunctionalization. Here, we investigate genic variation in epigenome-associated polymorphism rates in Arabidopsis thaliana and consider whether these affect the evolution of gene duplicates.

New insights into the pathogenicity of TMEM165 variants using structural modeling based on AlphaFold 2 predictions.

TMEM165 is a Golgi protein playing a crucial role in Mn transport, and whose mutations in patients are known to cause Congenital Disorders of Glycosylation. Some of those mutations affect the highly-conserved consensus motifs E-φ-G-D-[KR]-[TS] characterizing the CaCA2/UPF0016 family, presumably important for the transport of Mn which is essential for the function of many Golgi glycosylation enzymes. Others, like the G>R mutation, are far away from these motifs in the sequence.

What is the potential impact of genetic divergence of plastid ribosomal genes between lineages in hybrids? An approach using the 3D structure of the plastid ribosome.

Introduction: Following the integration of cyanobacteria into the eukaryotic cells, many genes were transferred from the plastid to the nucleus. As a result, plastid complexes are encoded both by plastid and nuclear genes. Tight co-adaptation is required between these genes as plastid and nuclear genomes differ in several characteristics, such as mutation rate and inheritance patterns.

Polluted wetlands contain multidrug-resistance plasmids encoding CTX-M-type extended-spectrum β-lactamases.

While most detailed analyses of antibiotic resistance plasmids focus on those found in clinical isolates, less is known about the vast environmental reservoir of mobile genetic elements and the resistance and virulence factors they encode. We selectively isolated three strains of cefotaxime-resistant Escherichia coli from a wastewater-impacted coastal wetland. The cefotaxime-resistant phenotype was transmissible to a lab strain of E.

Causes of Mutation Rate Variability in Plant Genomes.

Mutation is the source of all heritable diversity, the essential material of evolution and breeding. While mutation rates are often regarded as constant, variability in mutation rates has been observed at nearly every level-varying across mutation types, genome locations, gene functions, epigenomic contexts, environmental conditions, genotypes, and species. This mutation rate variation arises from differential rates of DNA damage, repair, and transposable element activation and insertion that together produce what is measured by DNA mutation rates.

-Glycan on the Non-Consensus N-X-C Glycosylation Site Impacts Activity, Stability, and Localization of the Sd Synthase B4GALNT2.

The Sd carbohydrate epitope and its biosynthetic B4GALNT2 enzyme are expressed in the healthy colon and down-regulated to variable extents in colon cancer. The human gene drives the expression of a long and a short protein isoform (LF-B4GALNT2 and SF-B4GALNT2) sharing identical transmembrane and luminal domains. Both isoforms are trans-Golgi proteins and the LF-B4GALNT2 also localizes to post-Golgi vesicles thanks to its extended cytoplasmic tail.

Critical Assessment of Methods for Predicting the 3D Structure of Proteins and Protein Complexes.

Advances in a scientific discipline are often measured by small, incremental steps. In this review, we report on two intertwined disciplines in the protein structure prediction field, modeling of single chains and modeling of complexes, that have over decades emulated this pattern, as monitored by the community-wide blind prediction experiments CASP and CAPRI. However, over the past few years, dramatic advances were observed for the accurate prediction of single protein chains, driven by a surge of deep learning methodologies entering the prediction field.

Better governance starts with better words: why responsible human tissue research demands a change of language.

The rise of precision medicine has led to an unprecedented focus on human biological material in biomedical research. In addition, rapid advances in stem cell technology, regenerative medicine and synthetic biology are leading to more complex human tissue structures and new applications with tremendous potential for medicine. While promising, these developments also raise several ethical and practical challenges which have been the subject of extensive academic debate.

Aquatic Flaviviruses.

Flaviviruses are positive-sense single-stranded RNA viruses, including some well-known human pathogens such as Zika, dengue, and yellow fever viruses, which are primarily associated with mosquito and tick vectors. The vast majority of flavivirus research has focused on terrestrial environments; however, recent findings indicate that a range of flaviviruses are also present in aquatic environments, both marine and freshwater. These flaviviruses are found in various hosts, including fish, crustaceans, molluscs, and echinoderms.

TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells.

Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments.

DNA Aptamers Block the Receptor Binding Domain at the Spike Protein of SARS-CoV-2.

DNA aptamers are versatile molecular species obtained by the folding of short single-stranded nucleotide sequences, with highly specific recognition capabilities against proteins. Here we test the ability of DNA aptamers to interact with the spike (S-)protein of the SARS-CoV-2 viral capsid. The S-protein, a trimer made up of several subdomains, develops the crucial function of recognizing the ACE2 receptors on the surface of human cells, and subsequent fusioning of the virus membrane with the host cell membrane.

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment.

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers).

Centrality Measures in Residue Interaction Networks to Highlight Amino Acids in Protein-Protein Binding.

Residue interaction networks (RINs) describe a protein structure as a network of interacting residues. Central nodes in these networks, identified by centrality analyses, highlight those residues that play a role in the structure and function of the protein. However, little is known about the capability of such analyses to identify residues involved in the formation of macromolecular complexes.

-GlcNAcylation Prediction: An Unattained Objective.

Background: -GlcNAcylation is an essential post-translational modification (PTM) in mammalian cells. It consists in the addition of a -acetylglucosamine (GlcNAc) residue onto serines or threonines by an -GlcNAc transferase (OGT). Inhibition of OGT is lethal, and misregulation of this PTM can lead to diverse pathologies including diabetes, Alzheimer's disease and cancers.