Learning torus PCA-based classification for multiscale RNA correction with application to SARS-CoV-2

Three-dimensional RNA structures frequently contain atomic clashes. Usually, corrections approximate the biophysical chemistry, which is computationally intensive and often does not correct all clashes. We propose fast, data-driven reconstructions from clash-free benchmark data with two-scale shape analysis: microscopic (suites) dihedral backbone angles, mesoscopic sugar ring centre landmarks. Our analysis relates concentrated mesoscopic scale neighbourhoods to microscopic scale clusters, correcting within-suite-backbone-to-backbone clashes exploiting angular shape and size-and-shape Frechet means. Validation shows that learned classes highly correspond with literature clusters and reconstructions are well within physical resolution. We illustrate the power of our method using cutting-edge SARS-CoV-2 RNA.

Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution, new validation tools, and implications for the future.

As a discipline, structural biology has been transformed by the three-dimensional electron microscopy (3DEM) "Resolution Revolution" made possible by convergence of robust cryo-preservation of vitrified biological materials, sample handling systems, and measurement stages operating a liquid nitrogen temperature, improvements in electron optics that preserve phase information at the atomic level, direct electron detectors (DEDs), high-speed computing with graphics processing units, and rapid advances in data acquisition and processing software. 3DEM structure information (atomic coordinates and related metadata) are archived in the open-access Protein Data Bank (PDB), which currently holds more than 11,000 3DEM structures of proteins and nucleic acids, and their complexes with one another and small-molecule ligands (~ 6% of the archive). Underlying experimental data (3DEM density maps and related metadata) are stored in the Electron Microscopy Data Bank (EMDB), which currently holds more than 21,000 3DEM density maps. After describing the history of the PDB and the Worldwide Protein Data Bank (wwPDB) partnership, which jointly manages both the PDB and EMDB archives, this review examines the origins of the resolution revolution and analyzes its impact on structural biology viewed through the lens of PDB holdings. Six areas of focus exemplifying the impact of 3DEM across the biosciences are discussed in detail (icosahedral viruses, ribosomes, integral membrane proteins, SARS-CoV-2 spike proteins, cryogenic electron tomography, and integrative structure determination combining 3DEM with complementary biophysical measurement techniques), followed by a review of 3DEM structure validation by the wwPDB that underscores the importance of community engagement.

Structural variable validation of an Online Learning Response Behavior (OLRB) instrument: A comparison analysis of three extraction methods of Exploratory Factor Analysis

Purpose>Measuring internal response of online learning is seen as fundamental to absorptive capacity which stimulates knowledge assimilation. However, the evaluation of practice and research of validated instruments that could effectively measure online learning response behavior is limited. Thus, in this study, a new instrument was designed based on literature to determine the structural variables that exist in the online learning response behavior.Design/methodology/approach>A structured survey was designed and distributed to 410 Malaysian students enrolled in higher-education institutions. The questionnaire has 38 items, all of which were scored using a seven-point likert scale. To begin with, exploratory factor analysis with three types of extraction methods (i.e. principal component, principal axis factoring and maximum likelihood) was used as the method for comparing the outcomes of each extraction method's grouping variables by constantly using a varimax rotation method. In the second phase, reliability analysis was performed to determine the reliability level of the grouping variables, and finally, correlation analysis was performed to determine the discriminant nomological validity of the grouping variables.Findings>The findings revealed that nine grouping variables were retrieved, with all items having a good value of factor loading and communalities, as well as an adequate degree of reliability. These extracted variables have good discriminant and nomological validity, as evidenced by correlation analysis, which confirmed that the directions of relationships among the extracted dimensions follow the expected theory (i.e. positive direction) and the correlation coefficient is less than 0.70.Research limitations/implications>This study proposes a comprehensive set of questionnaires that measure the student's online learning response behavior. These questionnaires have been developed on the basis of an extensive literature review and have undergone a rigorous process of validity and reliability for the purpose of enhancing students' online learning response behavior.Originality/value>This study's findings will aid academic practitioners in assessing the online learning response behavior of students, as well as enhancing the questionnaire's boost factor when administered in an online learning environment.

Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure

Objectives: This study aimed to model the changes resulting from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure. Methods: Genome sequence information of SARS CoV-2-infected patients located in Turkey was obtained from the GISAID EpiCoV database. Structural analysis of spike proteins was done using bioinformatics tools (MAFFT, PSIPRED, ProMod3, PyMoL and DynOmics). Results: We identified 76 Thr>Ile mutations in the N-terminal domain;468 Ile>Val mutations in the receptor binding site and 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val and 772 Val>Ile mutations in the S1 subunit. It has been observed that the mutations, except those of residues 771 and 772, may cause significant conformational, topological and electrostatic changes in a protein quaternary structure. It has been determined that the mutations in the receptor binding site transform the protein structure into a formation that can mask the binding site and affect receptor affinity. Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.

Covid-19.bioreproducibility.org: A web resource for SARS-CoV-2-related structural models.

The COVID-19 pandemic has triggered numerous scientific activities aimed at understanding the SARS-CoV-2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X-ray, cryo-EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert-verified information about SARS-CoV-2-related macromolecular models. In this article, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein.