mmCIF File Research Articles

Image-centric compression of protein structures improves space savings

BackgroundBecause of the rapid generation of data, the study of compression algorithms to reduce storage and transmission costs is important to bioinformaticians. Much of the focus has been on sequence data, including both genomes and protein amino acid sequences stored in FASTA files. Current standard practice is to use an ordinary lossless compressor such as gzip on a sequential list of atomic coordinates, but this approach expends bits on saving an arbitrary ordering of atoms, and it also prevents reordering the atoms for compressibility. The standard MMTF and BCIF file formats extend this approach with custom encoding of the coordinates. However, the brand new Foldcomp tool introduces a new paradigm of compressing local angles, to great effect. In this article, we explore a different paradigm, showing for the first time that image-based compression using global angles can also significantly improve compression ratios. To this end, we implement a prototype compressor ‘PIC’, specialized for point clouds of atom coordinates contained in PDB and mmCIF files. PIC maps the 3D data to a 2D 8-bit greyscale image and leverages the well developed PNG image compressor to minimize the size of the resulting image, forming the compressed file.ResultsPIC outperforms gzip in terms of compression ratio on proteins over 20,000 atoms in size, with a savings over gzip of up to 37.4% on the proteins compressed. In addition, PIC’s compression ratio increases with protein size.ConclusionImage-centric compression as demonstrated by our prototype PIC provides a potential means of constructing 3D structure-aware protein compression software, though future work would be necessary to make this practical.

BeEM: fast and faithful conversion of mmCIF format structure files to PDB format

BackgroundAlthough mmCIF is the current official format for deposition of protein and nucleic acid structures to the protein data bank (PDB) database, the legacy PDB format is still the primary supported format for many structural bioinformatics tools. Therefore, reliable software to convert mmCIF structure files to PDB files is needed. Unfortunately, existing conversion programs fail to correctly convert many mmCIF files, especially those with many atoms and/or long chain identifies.ResultsThis study proposed BeEM, which converts any mmCIF format structure files to PDB format. BeEM conversion faithfully retains all atomic and chain information, including chain IDs with more than 2 characters, which are not supported by any existing mmCIF to PDB converters. The conversion speed of BeEM is at least ten times faster than existing converters such as MAXIT and Phenix. Part of the reason for the speed improvement is the avoidance of conversion between numerical values and text strings.ConclusionBeEM is a fast and accurate tool for mmCIF-to-PDB format conversion, which is a common procedure in structural biology. The source code is available under the BSD licence at https://github.com/kad-ecoli/BeEM/.

RING-PyMOL: residue interaction networks of structural ensembles and molecular dynamics.

https://github.com/BioComputingUP/ring-pymol.

PrankWeb 3: accelerated ligand-binding site predictions for experimental and modelled protein structures.

Knowledge of protein-ligand binding sites (LBSs) enables research ranging from protein function annotation to structure-based drug design. To this end, we have previously developed a stand-alone tool, P2Rank, and the web server PrankWeb (https://prankweb.cz/) for fast and accurate LBS prediction. Here, we present significant enhancements to PrankWeb. First, a new, more accurate evolutionary conservation estimation pipeline based on the UniRef50 sequence database and the HMMER3 package is introduced. Second, PrankWeb now allows users to enter UniProt ID to carry out LBS predictions in situations where no experimental structure is available by utilizing the AlphaFold model database. Additionally, a range of minor improvements has been implemented. These include the ability to deploy PrankWeb and P2Rank as Docker containers, support for the mmCIF file format, improved public REST API access, or the ability to batch download the LBS predictions for the whole PDB archive and parts of the AlphaFold database.

PDBeCIF: an open-source mmCIF/CIF parsing and processing package

BackgroundBiomacromolecular structural data outgrew the legacy Protein Data Bank (PDB) format which the scientific community relied on for decades, yet the use of its successor PDBx/Macromolecular Crystallographic Information File format (PDBx/mmCIF) is still not widespread. Perhaps one of the reasons is the availability of easy to use tools that only support the legacy format, but also the inherent difficulties of processing mmCIF files correctly, given the number of edge cases that make efficient parsing problematic. Nevertheless, to fully exploit macromolecular structure data and their associated annotations such as multiscale structures from integrative/hybrid methods or large macromolecular complexes determined using traditional methods, it is necessary to fully adopt the new format as soon as possible.ResultsTo this end, we developed PDBeCIF, an open-source Python project for manipulating mmCIF and CIF files. It is part of the official list of mmCIF parsers recorded by the wwPDB and is heavily employed in the processes of the Protein Data Bank in Europe. The package is freely available both from the PyPI repository (http://pypi.org/project/pdbecif) and from GitHub (https://github.com/pdbeurope/pdbecif) along with rich documentation and many ready-to-use examples.ConclusionsPDBeCIF is an efficient and lightweight Python 2.6+/3+ package with no external dependencies. It can be readily integrated with 3rd party libraries as well as adopted for broad scientific analyses.

3D based on 2D: Calculating helix angles and stacking patterns using forgi 2.0, an RNA Python library centered on secondary structure elements.

We present forgi, a Python library to analyze the tertiary structure of RNA secondary structure elements. Our representation of an RNA molecule is centered on secondary structure elements (stems, bulges and loops). By fitting a cylinder to the helix axis, these elements are carried over into a coarse-grained 3D structure representation. Integration with Biopython allows for handling of all-atom 3D information. forgi can deal with a variety of file formats including dotbracket strings, PDB and MMCIF files. We can handle modified residues, missing residues, cofold and multifold structures as well as nucleotide numbers starting at arbitrary positions. We apply this library to the study of stacking helices in junctions and pseudoknots and investigate how far stacking helices in solved experimental structures can divert from coaxial geometries.

3D based on 2D: Calculating helix angles and stacking patterns using forgi 2.0, an RNA Python library centered on secondary structure elements.

We present forgi, a Python library to analyze the tertiary structure of RNA secondary structure elements. Our representation of an RNA molecule is centered on secondary structure elements (stems, bulges and loops). By fitting a cylinder to the helix axis, these elements are carried over into a coarse-grained 3D structure representation. Integration with Biopython allows for handling of all-atom 3D information. forgi can deal with a variety of file formats including dotbracket strings, PDB and MMCIF files. We can handle modified residues, missing residues, cofold and multifold structures as well as nucleotide numbers starting at arbitrary positions. We apply this library to the study of stacking helices in junctions and pseudoknots and investigate how far stacking helices in solved experimental structures can divert from coaxial geometries.

3D based on 2D: Calculating helix angles and stacking patterns using forgi 2.0, an RNA Python library centered on secondary structure elements.

We present forgi, a Python library to analyze the tertiary structure of RNA secondary structure elements. Our representation of an RNA molecule is centered on secondary structure elements (stems, bulges and loops). By fitting a cylinder to the helix axis, these elements are carried over into a coarse-grained 3D structure representation. Integration with Biopython allows for handling of all-atom 3D information. forgi can deal with a variety of file formats including dotbracket strings, PDB and MMCIF files. We can handle modified residues, missing residues, cofold and multifold structures as well as nucleotide numbers starting at arbitrary positions. We apply this library to the study of stacking helices in junctions and pseudo knots and investigate how far stacking helices in solved experimental structures can divert from coaxial geometries.

RABDAM: quantifying specific radiation damage in individual protein crystal structures.

Radiation damage remains one of the major limitations to accurate structure determination in protein crystallography (PX). Despite the use of cryo-cooling techniques, it is highly probable that a number of the structures deposited in the Protein Data Bank (PDB) have suffered substantial radiation damage as a result of the high flux densities of third generation synchrotron X-ray sources. Whereas the effects of global damage upon diffraction pattern reflection intensities are readily detectable, traditionally the (earlier onset) site-specific structural changes induced by radiation damage have proven difficult to identify within individual PX structures. More recently, however, development of the BDamage metric has helped to address this problem. BDamage is a quantitative, per-atom metric identifies potential sites of specific damage by comparing the atomic B-factor values of atoms that occupy a similar local packing density environment in the structure. Building upon this past work, this article presents a program, RABDAM, to calculate the BDamage metric for all selected atoms within any standard-format PDB or mmCIF file. RABDAM provides several useful outputs to assess the extent of damage suffered by an input PX structure. This free and open-source software will allow assessment and improvement of the quality of PX structures both previously and newly deposited in the PDB.

AceDRG: a stereochemical description generator for ligands.

The program AceDRG is designed for the derivation of stereochemical information about small molecules. It uses local chemical and topological environment-based atom typing to derive and organize bond lengths and angles from a small-molecule database: the Crystallography Open Database (COD). Information about the hybridization states of atoms, whether they belong to small rings (up to seven-membered rings), ring aromaticity and nearest-neighbour information is encoded in the atom types. All atoms from the COD have been classified according to the generated atom types. All bonds and angles have also been classified according to the atom types and, in a certain sense, bond types. Derived data are tabulated in a machine-readable form that is freely available from CCP4. AceDRG can also generate stereochemical information, provided that the basic bonding pattern of a ligand is known. The basic bonding pattern is perceived from one of the computational chemistry file formats, including SMILES, mmCIF, SDF MOL and SYBYL MOL2 files. Using the bonding chemistry, atom types, and bond and angle tables generated from the COD, AceDRG derives the `ideal' bond lengths, angles, plane groups, aromatic rings and chirality information, and writes them to an mmCIF file that can be used by the refinement program REFMAC5 and the model-building program Coot. Other refinement and model-building programs such as PHENIX and BUSTER can also use these files. AceDRG also generates one or more coordinate sets corresponding to the most favourable conformation(s) of a given ligand. AceDRG employs RDKit for chemistry perception and for initial conformation generation, as well as for the interpretation of SMILES strings, SDF MOL and SYBYL MOL2 files.

Real-Time Interactive Visualisation of Large Macromolecular Assemblies and Molecular Machines at Atomic Resolution

Recent advances in Cryo-EM and other structure determination techniques enabled a rapid increase in the complexity and size of biomacromolecular structures available in the Protein Data Bank (PDB). A great challenge is to deliver and visualize this data to the user in a reasonable time. Until now, Java-based applets such as Jmol have served this purpose. However, the lack of support for Java applets in the web browsers and introduction of HTML5 and WebGL web frameworks provide an opportunity to develop better solutions to address this problem.We have developed a comprehensive solution for both efficient delivery of large data sets and interactive visualisation of macromolecular structures.The CoordinateServer (https://www.ebi.ac.uk/pdbe/coordinates) provides functionality for dynamic selection of a subset of structural data (backbone, ligand binding sites, etc.) that is of interest to the user. The amount of transferred data is further reduced using binary representation of the standard mmCIF data format called BinaryCIF. The CoordinateServer thus provides a complete solution for efficient transfer of data to user interface.LiteMol (http://ncbr.muni.cz/LiteMol) is an interactive browser based 3D viewer, designed using HTML5 and WebGL technologies that provides all key structural visualisation modes. The viewer also integrates PDBe REST API services (http://pdbe.org/api) to show biomacromolecular annotations (validation, sequence annotation). LiteMol can use the standard mmCIF files or the CoordinateServer for fast data access. Thanks to integration with the CoordinateServer, LiteMol can generate an interactive 3D display for the largest currently available structure, the HIV capsid with 2.4 million atoms, in less than a minute. LiteMol is integrated into PDBe entry pages (e.g. http://www.ebi.ac.uk/pdbe/entry/pdb/1cbs/bound/REA) and can, for the first time, show the electron density maps online in an interactive way. We are collaborating with UniProt, OpenTargets, and Glycopedia teams to integrate LiteMol into their pages.

Big changes are ahead – a new format for crystallization communications inActa Cryst. F

The coming year 2014 will be an important year for crystallography as the scientific community throughout the world celebrates the International Year of Crystallography. Acta Cryst. F will commemorate this special event with a series of articles defining the current state-of-the-art in macromolecular crystallization, with one article appearing per month throughout 2014 and into 2015. We expect this series to be a useful resource for our readership and the wider structural biology community alike. Stay tuned. We have also been working diligently over the past two or three years to finalize new requirements and a new format for our regular articles. Maybe some of you have attended the presentations given by us at various meetings or workshops about the publication tool publBio (http://publbio.iucr.org). publBio is designed to make the preparation and submission of an article much more simple and straightforward than ever before, be it a structural or a crystallization communication. The latest version not only guides authors through the requirements for each article type but also provides a means of submitting the article directly to Acta Cryst. F, thus simplifying the first stages of the submission process. The IUCr Word template now also has some of the functionality of publBio and, just like publBio, offers the option of utilizing data from an existing PDB deposition or an mmCIF file when creating the tables in your article. In July this year, we published a contribution by Janet Newman and colleagues entitled Crystallization reports are the backbone of Acta F, but do they have any spine? (Newman et al., 2013 ▶; Weiss & Einspahr, 2013 ▶). The central message of this paper was that the information content of crystallization communications published in Acta Cryst. F varies widely. While this may not seem troubling at first glance, the notion that as many as 60% of these articles lack some essential information sparked some concern. With publBio, we have a tool that will allow us to address this issue efficiently and effectively, and that will also make a major contribution to correcting the problem. We feel that the time has come to take advantage of this by making publBio (or its counterpart in the IUCr Word template) mandatory for writing and submitting crystallization communications from 1 January 2014. We expect that you will enjoy working with publBio and we are looking forward to working with you to refine and improve it. From our perspective, another major advance is that publBio will make clear exactly what data are needed for an acceptable crystallization communication. There will of course be situations in which certain data items may not be necessary or may be unavailable, but these ‘exceptions to the rules’ are exactly those about which authors need to confer with Co-editors. Therefore, we ask our authors to make full use of publBio to ease the burden of creating their publications. Finally, we thank our authors for their continued support of our journal and wish you all Season’s Greetings and Happy Holidays. We look forward to 2014 with anticipation of all the new things this New Year will bring.

MmView: a web-based viewer of the mmCIF format

BackgroundStructural biomolecular data are commonly stored in the PDB format. The PDB format is widely supported by software vendors because of its simplicity and readability. However, the PDB format cannot fully address many informatics challenges related to the growing amount of structural data. To overcome the limitations of the PDB format, a new textual format mmCIF was released in June 1997 in its version 1.0. mmCIF provides extra information which has the advantage of being in a computer readable form. However, this advantage becomes a disadvantage if a human must read and understand the stored data. While software tools exist to help to prepare mmCIF files, the number of available systems simplifying the comprehension and interpretation of the mmCIF files is limited.FindingsIn this paper we present mmView - a cross-platform web-based application that allows to explore comfortably the structural data of biomacromolecules stored in the mmCIF format. The mmCIF categories can be easily browsed in a tree-like structure, and the corresponding data are presented in a well arranged tabular form. The application also allows to display and investigate biomolecular structures via an integrated Java application Jmol.ConclusionsThe mmView software system is primarily intended for educational purposes, but it can also serve as a useful research tool. The mmView application is offered in two flavors: as an open-source stand-alone application (available from http://sourceforge.net/projects/mmview) that can be installed on the user's computer, and as a publicly available web server.

Laboratory Communications inActa Crystallographica Section F

The last year has seen a number of enhancements to our still very young journal, Acta Cryst. F. There was, for instance, the introduction of a tool for creating interactive figures (Einspahr & Guss, 2008b ▶) which can then be included in journal articles. The first Acta Cryst. F paper with such an enhanced figure was published by Mueller-Dieckmann et al. (2008 ▶). Also introduced was the ability to upload an mmCIF file (obtained upon depositing coordinate and structure-factor amplitude files with the PDB, for example) and create experimental details tables (or even a complete article) for publication (Einspahr & Weiss, 2008 ▶). We have also invited the NMR community to publish structures in Acta Cryst. F and devised an updated set of standards for this purpose (Einspahr & Guss, 2008a ▶). More information on these standards can be found at http://journals.iucr.org/services/nmr/nmrmeetingsummary.html. Another enhancement is the introduction of a new category of papers to Acta Cryst. F, Laboratory Communications. In parallel with the categories of Structural Communications and Crystallization Communications, this new category is for papers that describe special methods, equipment modifications, techniques for accomplishing certain tasks etc. that are related to crystallization or other fields of structural biology. The papers we want to attract contain observations made in the laboratory that are likely to be useful to our readers. Very often, these observations range from tips and tricks to novel procedures or adaptations that are hidden in the methods paragraphs of long papers, or may not be published at all. Our aim is to collect these for Acta Cryst. F and make them accessible to our readers. This issue contains the first example of a paper in the Laboratory Communications category by Tobias Beck and colleagues (Beck et al., 2009 ▶) and is titled How to get the magic triangle and the MAD triangle into your protein crystal. It describes the practical aspects of handling the compounds I3C (also known as the magic triangle) and B3C (the MAD triangle) for derivatizing protein crystals and phase determination. As an example, orthorhombic crystals of the serine protease trypsin were derivatized by co-crystallization with B3C. The paper conforms exactly to the spirit of the new category in the sense that it describes a successful experiment in sufficient detail so that it can be reproduced by others and, more importantly, that it can be applied to other problems. We hope that this new category will serve our readers well and we would like to invite you to write up your observations and submit them to Acta Cryst. F.

Deposit3D: a tool for automating structure depositions to the Protein Data Bank.

Almost all successful protein structure-determination projects in the public sector culminate in a structure deposition to the Protein Data Bank (PDB). In order to expedite the deposition process, Deposit3D has been developed. This command-line script calculates or gathers all the required structure-deposition information and outputs this data into a mmCIF file for subsequent upload through the RCSB PDB ADIT interface. Deposit3D might be particularly useful for structural genomics pipeline projects because it allows workers involved with various stages of a structure-determination project to pool their different categories of annotation information before starting a deposition session.