In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, PubMed, PubMed Central, LocusLink, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SARS Coronavirus Resource, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov.

/pdf/database-resources-of-the-national-center-for-biotechnology-36jlaw3fxd.pdf

Database resources of the National Center for Biotechnology Information

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.

Phyre2 is a web-based tool for predicting and analyzing protein structure and function. Phyre2 uses advanced remote homology detection methods to build 3D models, predict ligand binding sites, and analyze amino acid variants in a protein sequence. Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2
 . A typical structure prediction will be returned between 30 min and 2 h after submission.

/pdf/the-phyre2-web-portal-for-protein-modeling-prediction-and-xppnx59tej.pdf

The Phyre2 web portal for protein modeling, prediction and analysis

TBtools: An Integrative Toolkit Developed for Interactive Analyses of Big Biological Data.

Determining the structure and function of a novel protein is a cornerstone of many aspects of modern biology. Over the past decades, a number of computational tools for structure prediction have been developed. It is critical that the biological community is aware of such tools and is able to interpret their results in an informed way. This protocol provides a guide to interpreting the output of structure prediction servers in general and one such tool in particular, the protein homology/analogy recognition engine (Phyre). New profile–profile matching algorithms have improved structure prediction considerably in recent years. Although the performance of Phyre is typical of many structure prediction systems using such algorithms, all these systems can reliably detect up to twice as many remote homologies as standard sequence-profile searching. Phyre is widely used by the biological community, with >150 submissions per day, and provides a simple interface to results. Phyre takes 30 min to predict the structure of a 250-residue protein.

/pdf/protein-structure-prediction-on-the-web-a-case-study-using-42dp65897s.pdf

Protein structure prediction on the Web: a case study using the Phyre server.

Protein interactions have evolved into highly precise and regulated networks adding an immense layer of complexity to cellular systems. The most accurate atomistic description of protein binding sites can be obtained directly from structures of protein complexes. The availability of structurally characterized protein interfaces significantly improves our understanding of interactomes, and the progress in structural characterization of protein-protein interactions (PPIs) can be measured by calculating the structural coverage of protein domain families. We analyze the coverage of protein domain families (defined according to CDD and Pfam databases) by structures, structural protein-protein complexes and unique protein binding sites. Structural PPI coverage of currently available protein families is about 30% without any signs of saturation in coverage growth dynamics. Given the current growth rates of domain databases and structural PPI deposition, complete domain coverage with PPIs is not expected in the near future. As a result of this study we identify families without any protein-protein interaction evidence (listed on a supporting website http://www.ncbi.nlm.nih.gov/Structure/ibis/coverage/) and propose them as potential targets for structural studies with a focus on protein interactions.

Coverage of protein domain families with structural protein–protein interactions: Current progress and future trends

The VAST+ algorithm is an efficient, simple, and elegant solution to the problem of comparing the atomic structures of biological assemblies. Given two protein assemblies, it takes as input all the pairwise structural alignments of the component proteins. It then clusters the rotation matrices from the pairwise superpositions, with the clusters corresponding to subsets of the two assemblies that may be aligned and well superposed. It uses the Vector Alignment Search Tool (VAST) protein-protein comparison method for the input structural alignments, but other methods could be used, as well. From a chosen cluster, an "original" alignment for the assembly may be defined by simply combining the relevant input alignments. However, it is often useful to reduce/trim the original alignment, using a Monte Carlo refinement algorithm, which allows biologically relevant conformational differences to be more readily detected and observed. The method is easily extended to include RNA or DNA molecules. VAST+ results may be accessed via the URL https://www.ncbi.nlm.nih.gov/Structure , then entering a PDB accession or terms in the search box, and using the link [VAST+] in the upper right corner of the Structure Summary page.

/pdf/biological-assembly-comparison-with-vast-3b9fqkse47.pdf

Biological Assembly Comparison with VAST.

Summary iCn3D (l-see-in-3D) is a web-based 3D molecular structure viewer implemented in JavaScript. It invites users to explore sequence-structure relationships by displaying 3D structures, protein and nucleotide sequences, and biological annotations such as protein domains, Single Nucleotide Variations, functional sites, molecular contacts, as well as user defined features. Customized and user-annotated displays can be shared with colleagues or publishers via a simple URL, or embedded in web pages as live 3D displays. iCn3D is unique in its ability to simultaneously show 3D structure, 2D molecular networks and interactions, and 1D protein and nucleotide sequences through an integrated sequence/annotation browser. Arbitrary molecular features can be selected in any of the 1D/2D/3D windows as sets of molecules or residues, utilizing flexible user interfaces. These selections are synchronized dynamically in all displays. They can, for example, be shown as tracks in the 1D sequence/annotation browser with simultaneous 3D representations. They can be saved and reused throughout a single user session, or exported for subsequent sessions and further external analysis. iCn3D is rich in structural analysis and visualization features and has a built-in user interface that supports both command line- and menu-driven operation. Session commands can be saved, replayed and shared. iCn3D can display superimposed structures obtained from NCBFs VAST+ structural alignment resource, for comparative analysis of tertiary or quaternary structure. iCn3D can also display electron density maps for crystal structures and export files for 3D printing. The following example URL exemplifies some of the 1D/2D/3D representations: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?mmdbid=1TUP&showanno=1&show2d=1&showsets=1. Availability and implementation iCn3D is freely available to the public. Its source code is available at https://github.com/ncbi/icn3d.

https://biorxiv.org/content/biorxiv/early/2018/12/19/501692.full-text.pdf

iCn3D, a Web-based 3D Viewer for the Visualization of Biomolecular Structure and Sequence Annotation

Summary iCn3D (I-see-in-3D) is a web-based 3D molecular structure viewer focusing on the interactive structural analysis. It can simultaneously show 3D structure, 2D molecular contacts, and 1D protein and nucleotide sequences through an integrated sequence/annotation browser. Pre-defined and arbitrary molecular features can be selected in any of the 1D/2D/3D windows as sets of residues and these selections are synchronized dynamically in all displays. Biological annotations such as protein domains, single nucleotide variations, etc. can be shown as tracks in the 1D sequence/annotation browser. These customized displays can be shared with colleagues or publishers via a simple URL. iCn3D can display structure-structure alignment obtained from NCBI’s VAST+ service. It can also display the alignment of a sequence with a structure as identified by BLAST, and thus relate 3D structure to a large fraction of all known proteins. iCn3D can also display electron density maps or electron microscopy (EM) density maps, and export files for 3D printing. The following example URL exemplifies some of the 1D/2D/3D representations: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?mmdbid=1TUP&showanno=1&show2d=1&showsets=1. Availability and implementation iCn3D is freely available to the public. Its source code is available at https://github.com/ncbi/icn3d. Supplementary information User instructions are available at Bioinformatics online

https://www.biorxiv.org/content/biorxiv/early/2019/05/03/501692.full.pdf

Dachuan Zhang

Papers

Coverage of protein domain families with structural protein–protein interactions: Current progress and future trends

Biological Assembly Comparison with VAST.

iCn3D, a Web-based 3D Viewer for the Visualization of Biomolecular Structure and Sequence Annotation

iCn3D, a Web-based 3D Viewer for Sharing 1D/2D/3D Representations of Biomolecular Structures

Abstract 1363: iCn3D, a Platform to Align and Annotate AlphaFold Structures