Locally Developed Software and Resources
Good computer programs have always been vitally important to the work of the LMB. Many of the groups here write, or contribute to scientific software, and wherever possible this work is released to the open source software community.
Bioinformatics
Protein Contacts Atlas – a tool that helps biologists analyse and visualise protein structures at atomic resolution using residue-residue contact networks, developed by Melis Kayikci, AJ Venkatakrishnan, and M Madan Babu. Visualisations of biomolecular structures allow researchers to gain insights into biological functions and generate testable hypotheses. Typical visualisations primarily depict covalent bonds only and not other, non-covalent, contacts between atoms. However the structure also depends on these non-covalent contacts, thereby they effect physiological function, pathogenesis, and drug action. The Protein Contacts Atlas is an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures that provides a range of representations and properties by which individual residues can be studied.
SCOP – Structural Classification of Proteins. Nearly all proteins have structural similarities with other proteins and, in some of these cases, share a common evolutionary origin. The SCOP database, created by manual inspection and abetted by a battery of automated methods, aims to provide a detailed and comprehensive description of the structural and evolutionary relationships between all proteins whose structure is known.
SUPERFAMILY – A database of structural and functional annotation for all proteins and genomes. Julian Gough’s Computational Genomics Group has produced a range of software and resources that span the scales of biology from DNA, proteins, interactions, networks, and cells, up to whole organism phenotypes. The full list of software and resources managed by the Computational Genomics Group can be found on their group page.
Cellular imaging and neuroscience
Fiji – an image processing package based on NIH’s ImageJ – Contributions by Gregory Jefferis’ group, targeting the tools towards 3D analysis of biological images especially brains.
NeuroAnatomy Toolbox – a large suite of R packages for analysis of neuronal morphology (including the NBLAST tool), 3D density data describing neuronal projections, image registration within and across different template brains and analysis of electron microscopy connectomics data (including interfaces to the CATMAID and neuPrint tools). Open source development on GitHub by Gregory Jefferis’ group and further described at natverse.org. Additional software and experimental resources are described on the Jefferis group website.
SARFIA (Semi-Automated Routines for Functional Image Analysis) – developed by Mario Dorostkar for the analysis of functional fluorescence data, for instance recordings from cells labeled with fluorescent calcium indicators. However, it allows access to a variety of inbuilt and custom-written image processing functions. Key features are image-based detection of structures of interest using the Laplace operator, determining the positions of units in a layered network, clustering algorithms to classify units with similar functional responses, and a database to store, exchange and analyse results across experiments. GUI access to a wide range of analysis functions for image stacks. The custom image processing functions include thresholding based on the Laplace operator, filtering of 3D waves using principal component analysis (PCA), rotating functions, images/image stacks without interpolation, line scan analysis; Automated baseline detection, hierarchical clustering and bleach subtraction from fluorescence traces. The package includes a manual describing the control panels and a help file that describes all functions in detail. SARFIA is available for Igor Pro on the Igor Exchange. The core thresholding and data extraction functions are also available for Matlab on Matlab Central.
Structural biology
AceDRG (Fei Long) – stereo-chemical description generator for monomers/ligands. Encapsulates information about local chemical and topological environments derived from a small molecule database (the Crystallography Open Database), and uses this information to derive ideal bond lengths, angles, etc. for an unknown monomer/ligand. AceDRG can also generate link information to encapsulate a covalent bond between two monomers. More information about this software can be found on the Computational Structural Biology Group website.
AIMLESS (Phil Evans) – scales symmetry-related intensities together to correct for differences in their measurement methods, averages them and produces a large variety of statistics indicating the data quality.
BALBES (Fei Long) – automatic molecular replacement pipeline. A system for solving protein structures using x-ray crystallographic data, which aims to integrate all components necessary for finding a solution structure by molecular replacement. It comprises a database, scientific programs and a python pipeline. The system is automated so that it needs no user intervention when running a complicated combination of jobs such as model searching, molecular replacement and refinement. More information about this software can be found on the Computational Structural Biology Group website.
Coot (Paul Emsley) – Crystallographic Object-Oriented Toolkit. For macromolecular model building, model completion and validation, particularly suitable for protein modelling using MX and cryo-EM data. Coot displays maps and models and allows model manipulations such as idealization, real space refinement, manual rotation/translation, rigid-body fitting, ligand search, solvation, mutations, rotamers, Ramachandran plots, skeletonization, non-crystallographic symmetry and more. More information about this software can be found on the Computational Structural Biology Group website.
cryoEF – An open-source software package for analysis of the orientation distribution of cryo-electron microscopy data, developed by Christopher Russo and Katerina Naydenova. The orientation distribution of a single-particle electron cryo-microscopy specimen can limit the resolution of the reconstructed density map if the particles are not randomly oriented on the support surface. This method describes the quality of an orientation distribution in terms of providing uniform resolution in all directions, by a single number – the efficiency. The cryoEF program will assist you in determining to what extent this affects the resolution of your 3D reconstruction.
EMDA (Rangana Warshamanage) – Electron Microscopy Data Analytical toolkit, is an importable Python library for Electron Microscopy map and model manipulations. EMDA tools can be divided into four basic categories. 1) tools for reading, writing and converting EM data in CCP4 MAP, MRC and MTZ formats, 2) tools for map and map-model validation based on FSC and local correlation, 3) tools that are based on maximum likelihood method and use some elements of Bayesian statistics for map improvement, and 4) other tools for general use such as map symmetry validation, difference map etc. More information about this software can be found in the latest documentation and on the Computational Structural Biology Group website.
LibG (Fei Long) – Generates restraints to stabilise refinement of DNA/RNA models during refinement. Restraints are generated for base-pairs, stacking planes, sugar puckers, and other torsion angles. More information about this software can be found on the Computational Structural Biology Group website.
LORESTR (Oleg Kovalevskiy) – LOw RESolution STRucture refinement pipeline. Executes multiple model refinement instances using different parameters in order to find the best protocol. Generates restraints using ProSMART and LibG, and refines models using REFMAC5. The pipeline performs auto-detection of twinning and selects the optimal scaling method and solvent parameters. Can either use user-supplied homologous structures, or run an automated BLAST search and download homologues from the PDB. More information about this software can be found on the Computational Structural Biology Group website.
MOSFLM (Andrew Leslie, Harry Powell) – indexes the diffraction pattern and produces integrated reflection intensities. An interactive graphical interface iMosflm makes this easy for the user.
MRC Image Processing Software – a collection of around 80 computer programs for processing 2D crystal and helical electron microscope images. The programs have been written by members of the LMB over the last 40 years in FORTRAN or C. The visualization and manipulation program Ximdisp is based on a home-written library of X-Windows subroutines. File reading/writing requirements for all the programs are provided by a subset of CCP4 subroutines in order to maintain compatibility with CCP4 MAPFORMAT. The package is distributed freely to academic users worldwide and further information can be found here. Please contact Richard Henderson for more information.
POINTLESS (Phil Evans) – determines the point group & space group symmetry from the list of intensities from MOSFLM.
ProSHADE (Michal Tykac) – PROtein SHApe DEscription and symmetry detection. Library and associated tool providing functionalities for computing shape-wise structural distances between pairs of molecules, detecting symmetry over the centre of mass of a single structure, map re-sizing, as well as matching density maps and coordinate models. More information about this software can be found on the Computational Structural Biology Group website.
ProSMART (Rob Nicholls) – PROcrustes Structural Matching Alignment and Restraints Tool. Designed for the conformation-independent comparison of macromolecular structural models, and the generation of external restraints for use during macromolecular refinement at low resolution. Restraints to reference structures, hydrogen bonding patterns, and generic self-restraints may be generated. Supports models corresponding to protein and nucleic acids, from MX and cryo-EM. More information about this software can be found on the Computational Structural Biology Group website.
REFMAC5 (Garib Murshodov) – REFinement of MACromolecular Structures. Use the Maximum Likelihood method and some elements of Bayesian Statistics to perform full model refinement and map calculation. Originally designed for use with data from MX, REFMAC5 has been adapted and extended to support data from other sources including cryo-EM. More information about this software can be found on the Computational Structural Biology Group website.
RELION (Regularised Likelihood OptimisatioN) – a stand-alone computer program for Maximum A Posteriori (MAP) refinement of (multiple) 3D reconstructions or 2D class averages in electron cryo-microscopy (cryo-EM). It is developed in the group of Sjors Scheres. Briefly, the ill-posed problem of 3D-reconstruction is regularised by incorporating prior knowledge: the fact that macromolecular structures are smooth, i.e. they have limited power in the Fourier domain. In the corresponding Bayesian framework, many parameters of a statistical model are learned from the data, which leads to objective and high-quality results without the need for user expertise. The underlying theory of MAP refinement is given in Scheres (2012) JMB. A more detailed description of its implementation is given in Scheres (2012) JSB.
SCOP – Structural Classification of Proteins. Nearly all proteins have structural similarities with other proteins and, in some of these cases, share a common evolutionary origin. The SCOP database, created by manual inspection and abetted by a battery of automated methods, aims to provide a detailed and comprehensive description of the structural and evolutionary relationships between all proteins whose structure is known.
TiltStats – An open-source software package for robust evaluation of biological electron microscopy data and validation of cryo-EM structures using tilt-pairs. The algorithms and code were developed by Christopher Russo and Lori Passmore.