RCSB Protein Data Bank: visualizing groups of experimentally determined PDB structures alongside computed structure models of proteins

Recent advances in Artificial Intelligence and Machine Learning (e.g., AlphaFold, RosettaFold, and ESMFold) enable prediction of three-dimensional (3D) protein structures from amino acid sequences alone at accuracies comparable to lower-resolution experimental methods. These tools have been employed to predict structures across entire proteomes and the results of large-scale metagenomic sequence studies, yielding an exponential increase in available biomolecular 3D structural information. Given the enormous volume of this newly computed biostructure data, there is an urgent need for robust tools to manage, search, cluster, and visualize large collections of structures. Equally important is the capability to efficiently summarize and visualize metadata, biological/biochemical annotations, and structural features, particularly when working with vast numbers of protein structures of both experimental origin from the Protein Data Bank (PDB) and computationally-predicted models. Moreover, researchers require advanced visualization techniques that support interactive exploration of multiple sequences and structural alignments. This paper introduces a suite of tools provided on the RCSB PDB research-focused web portal RCSB. org, tailor-made for efficient management, search, organization, and visualization of this burgeoning corpus of 3D macromolecular structure data

X-ray structures of two proteins belonging to Pfam DUF178 revealed unexpected structural similarity to the DUF191 Pfam family

<p>Abstract</p> <p>Background</p> <p>Pfam is a comprehensive collection of protein domains and families, with a range of well-established information including genome annotation. Pfam has two large series of functionally uncharacterized families, known as Domains of Unknown Function (DUFs) and Uncharacterized Protein Families (UPFs).</p> <p>Results</p> <p>Crystal structures of two proteins from <it>Deinococcus radiodurans </it>and <it>Streptomyces coelicolor </it>belonging to Pfam protein family DUF178 (ID: PF02621) have been determined using Selenium-Single-wavelength Anomalous Dispersion (Se-SAD). Based on the structure, we have identified the putative function for this family of protein.</p> <p>Conclusion</p> <p>Unexpectedly, we found that DUF178 Pfam is remarkably similar to Pfam family DUF191 suggesting that the sequence-based classification alone may not be sufficient to classify proteins into Pfam families.</p

A Search for Stars of Very Low Metal Abundance. VI. Detailed Abundances of 313 Metal-Poor Stars

We present radial velocities, equivalent widths, model atmosphere parameters, and abundances or upper limits for 53 species of 48 elements derived from high resolution optical spectroscopy of 313 metal-poor stars. A majority of these stars were selected from the metal-poor candidates of the HK Survey of Beers, Preston, and Shectman. We derive detailed abundances for 61% of these stars for the first time. Spectra were obtained during a 10-year observing campaign using the Magellan Inamori Kyocera Echelle spectrograph on the Magellan Telescopes at Las Campanas Observatory, the Robert G. Tull Coude Spectrograph on the Harlan J. Smith Telescope at McDonald Observatory, and the High Resolution Spectrograph on the Hobby-Eberly Telescope at McDonald Observatory. We perform a standard LTE abundance analysis using MARCS model atmospheres, and we apply line-by-line statistical corrections to minimize systematic abundance differences arising when different sets of lines are available for analysis. We identify several abundance correlations with effective temperature. A comparison with previous abundance analyses reveals significant differences in stellar parameters, which we investigate in detail. Our metallicities are, on average, lower by approx. 0.25 dex for red giants and approx. 0.04 dex for subgiants. Our sample contains 19 stars with [Fe/H] < -3.5, 84 stars with [Fe/H] < -3.0, and 210 stars with [Fe/H] < -2.5. Detailed abundances are presented here or elsewhere for 91% of the 209 stars with [Fe/H] < -2.5 as estimated from medium resolution spectroscopy by Beers, Preston, and Shectman. We will discuss the interpretation of these abundances in subsequent papers.Comment: Accepted for publication in the Astronomical Journal. 60 pages, 59 figures, 18 tables. Machine-readable versions of the long tables can be found in the ancillary data file

NASA's Aeroacoustic Tools and Methods for Analysis of Aircraft Noise

Aircraft community noise is a significant concern due to continued growth in air traffic, increasingly stringent environmental goals, and operational limitations imposed by airport authorities. The ability to quantify aircraft noise at the source and ultimately at observers is required to develop low noise aircraft designs and flight procedures. Predicting noise at the source, accounting for scattering and propagation through the atmosphere to the observer, and assessing the perception and impact on a community requires physics-based aeroacoustics tools. Along with the analyses for aero-performance, weights and fuel burn, these tools can provide the acoustic component for aircraft MDAO (Multidisciplinary Design Analysis and Optimization). Over the last decade significant progress has been made in advancing the aeroacoustic tools such that acoustic analyses can now be performed during the design process. One major and enabling advance has been the development of the system noise framework known as Aircraft NOise Prediction Program2 (ANOPP2). ANOPP2 is NASA's aeroacoustic toolset and is designed to facilitate the combination of acoustic approaches of varying fidelity for the analysis of noise from conventional and unconventional aircraft. The toolset includes a framework that integrates noise prediction and propagation methods into a unified system for use within general aircraft analysis software. This includes acoustic analyses, signal processing and interfaces that allow for the assessment of perception of noise on a community. ANOPP2's capability to incorporate medium fidelity shielding predictions and wind tunnel experiments into a design environment is presented. An assessment of noise from a conventional and Hybrid Wing Body (HWB) aircraft using medium fidelity scattering methods combined with noise measurements from a model-scale HWB recently placed in NASA's 14x22 wind tunnel are presented. The results are in the form of community noise metrics and auralizations

Structural basis for activation of the therapeutic l-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase

l-nucleoside analogs represent an important class of small molecules for treating both viral infections and cancers. These pro-drugs achieve pharmacological activity only after enzyme-catalyzed conversion to their tri-phosphorylated forms. Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the l-nucleosides (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC)—an approved anti-human immunodeficiency virus (HIV) agent—and troxacitabine (TRO)—an experimental anti-neoplastic agent. The first step in activating these agents is catalyzed by dCK. Our studies reveal how dCK, which normally catalyzes phosphorylation of the natural d-nucleosides, can efficiently phosphorylate substrates with non-physiologic chirality. The capability of dCK to phosphorylate both d- and l-nucleosides and nucleoside analogs derives from structural properties of both the enzyme and the substrates themselves. First, the nucleoside-binding site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. Second, the pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the l- and d-enantiomeric forms to adopt similar shapes when bound to the enzyme. This is the first analysis of the structural basis for activation of l-nucleoside analogs, providing further impetus for discovery and clinical development of new agents in this molecular class

Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein

AbstractThe cocrystal structure of human poly(A)-binding protein (PABP) has been determined at 2.6 Å resolution. PABP recognizes the 3′ mRNA poly(A) tail and plays critical roles in eukaryotic translation initiation and mRNA stabilization/degradation. The minimal PABP used in this study consists of the N-terminal two RRM-type RNA-binding domains connected by a short linker (RRM1/2). These two RRMs form a continuous RNA-binding trough, lined by an antiparallel β sheet backed by four α helices. The polyadenylate RNA adopts an extended conformation running the length of the molecular trough. Adenine recognition is primarily mediated by contacts with conserved residues found in the RNP motifs of the two RRMs. The convex dorsum of RRM1/2 displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with translation initiation factors and regulatory proteins

The Abundances Of Neutron-Capture Species In The Very Metal-Poor Globular Cluster M15: A Uniform Analysis Of Red Giant Branch And Red Horizontal Branch Stars

The globular cluster M15 is unique in its display of star-to-star variations in the neutron-capture elements. Comprehensive abundance surveys have been previously conducted for handfuls of M15 red giant branch (RGB) and red horizontal branch (RHB) stars. No attempt has been made to perform a single, self-consistent analysis of these stars, which exhibit a wide range in atmospheric parameters. In the current effort, a new comparative abundance derivation is presented for three RGB and six RHB members of the cluster. The analysis employs an updated version of the line transfer code MOOG, which now appropriately treats coherent, isotropic scattering. The apparent discrepancy in the previously reported values for the metallicity of M15 RGB and RHB stars is addressed and a resolute disparity of Delta(RHB-RGB) approximate to 0.1 dex in the iron abundance was found. The anti-correlative behavior of the light neutron-capture elements (Sr, Y, Zr) is clearly demonstrated with both Ba and Eu, standard markers of the s- and r-process, respectively. No conclusive detection of Pb was made in the RGB targets. Consequently for the M15 cluster, this suggests that the main component of the s-process has made a negligible contribution to those elements normally dominated by this process in solar system material. Additionally for the M15 sample, a large Eu abundance spread is confirmed, which is comparable to that of the halo field at the same metallicity. These abundance results are considered in the discussion of the chemical inhomogeneity and nucleosynthetic history of M15.National Science Foundation AST 07-07447, AST 09-08978Astronom