The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs.

Two cytotoxic alkaloids, discorhabdins L (1) and I (2), were isolated from Latrunculia brevis and their structures assigned on the basis of detailed spectroscopic analysis and comparison with the known metabolites discorhabdins R (5), D (6), and B (4). Compounds 1 and 2 showed strong in vitro cytotoxicity against a panel of 14 tumor cell lines.

Motivation After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm. Results Using a curated collection of apo-holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions. Availability Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021 Supplementary Information Supplementary data is available at the journal's web site.

The sponge Spongia agaricina from Tarifa, Cadiz, Spain, contains two new 9,11-secosterols, [3-0-deacetylluffasterol B (1) and 3-0-deacetyl-22,23-dihydro-24,28-dehydroluffasterol B (2)] and two new sesterterpenoids [12,16-di-epi-12-0-deacetyl-16-0-acetylfuroscalarol (3) and 16-epi-scalarolbutenolide (4)], in addition to the known compounds 5-15. The structures of all compounds were elucidated by interpretation of' spectroscopic data. The metabolites 1-3 showed significant cytotoxicity against four tumor cell lines (C50 1 microgram/mL).

The sponge Cacospongia scalaris from Tarifa Island, Spain, contains in addition to five known compounds (1−5), the new scalarane sestertepenes 18-epi-scalaradial (6), 19-dihydroscalaradial (7), 12-epi-acetylscalarolide (8), and 16-acetylfuroscalarol (9) together with three uncommon norscalaranes norscalaral A (10), norscalaral B (11), and norscalaral C (12). The structures were elucidated by interpretation of spectral data. 18-epi-Scalaradial (6) represents the missing stereoisomer on structure−activity studies carried out with compounds of this series and did not react with methylamine. The new compounds isolated from C. scalaris showed significant in vitro cytotoxicity against five tumor cell lines with 18-epi-scalaradial showing the greatest activity (ED50 = 0.2 μg/mL).

This paper describes the attempts to protect and re-establish threatened populations of the native freshwater crayfish, Austropotamobius pallipes, of Navarra, Spain. Three species of crayfish are presently thriving in Navarra, the native species A. pallipes and the introduced North American species Pacifastacus leniusculus and Procambarus ciarkii. Both species are known to carry the fungus Aphanomyces astaci in their cuticles and to transmite it to the native species. The management strategies implemented by the authorities in order to restore native populations of crayfish are discussed.

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Human metapneumovirus, which belongs to the Paramyxoviridae family and has been classified as a member of the Pneumovirus genus, is genetically and clinically similar to other family members such as human respiratory syncytial virus. A total of 1146 nasopharyngeal aspirates from pediatric patients with moderate and severe acute lower respiratory tract infections, hospitalized at the Ricardo Gutierrez Childreńs Hospital (Buenos Aires, Argentina), were tested by real time RT-PCR for human metapneumovirus. Results showed that 168 (14.65%) were positive. Thirty-six of these 168 samples were randomly selected to characterize positive cases molecularly. The phylogenetic analysis of the sequences of the G and F genes showed that genotypes A2 and B2 cocirculated during 2009 and 2010 and that only genotype A2 circulated in 2011 in Argentina. Genotype A2 prevailed during the study period, a fact supported by a higher effective population size (Neτ) and higher diversity as compared to that of genotype B2 (10.9% (SE 1.3%) vs. 1.7% (SE 0.4%), respectively). The phylogeographic analysis of the G protein gene sequences showed that this virus has no geographical restrictions and can travel globally harbored in hosts. The selection pressure analysis of the F protein showed that although this protein has regions with polymorphisms, it has vast structural and functional constraints. In addition, the predicted B-linear epitopes and the sites recognized by previously described monoclonal antibodies were conserved in all Argentine sequences. This points out this protein as a potential candidate to be the target of future humanized antibodies or vaccines.