CCP-EM

CCP-EM
Name	CCP-EM
Developer	Collaborative Computational Project
Released	2012
Programming language	Python (programming language), C++
Operating system	Linux, macOS, Microsoft Windows
Genre	Bioinformatics, Structural biology
License	Open-source software

CCP-EM CCP-EM is a software suite for cryo-electron microscopy map interpretation, model building, and validation, developed as part of a collaborative initiative to support structural biologists using cryo-EM data. It integrates tools for map sharpening, map-model fitting, model refinement, and validation, interfacing with major packages used in macromolecular structure determination. The project cooperates with international laboratories and facilities to provide reproducible workflows for researchers working with electron microscopy maps and atomic models.

Overview

CCP-EM provides a collection of interoperable tools and graphical interfaces that link to established packages such as Phenix (software), REFMAC, Coot, RELION, CryoSPARC, and EMAN2 while supporting file formats used at European Molecular Biology Laboratory, Brookhaven National Laboratory, Lawrence Berkeley National Laboratory, Diamond Light Source, and Riken Center for Biosystems Dynamics Research. The suite includes programs for map preprocessing, map sharpening, density modification, flexible fitting, and model validation with connectors to databases like Protein Data Bank and Electron Microscopy Data Bank. CCP-EM aligns with community standards promoted by organizations such as International Union of Crystallography, Worldwide Protein Data Bank, and funding agencies including National Institutes of Health and European Research Council.

History and Development

Development began to consolidate methods from efforts at institutions including MRC Laboratory of Molecular Biology, University of Cambridge, University of Oxford, University College London, University of York, University of Manchester, and Diamond Light Source. Early contributors included developers from Collaborative Computational Project No. 4, Collaborative Computational Project No. 1, and research groups affiliated with Wellcome Trust. Key milestones involved integration with algorithms from Rossmann fold studies and methodologies adapted from X-ray crystallography packages such as CCP4. Community workshops at venues like Gordon Research Conferences, EMBO Workshop, Cold Spring Harbor Laboratory, and meetings at American Crystallographic Association helped shape the roadmap. Funding and collaborative agreements involved entities like Wellcome Trust, Biotechnology and Biological Sciences Research Council, European Molecular Biology Organization, and national infrastructures such as UK Research and Innovation.

Features and Components

The suite provides a graphical user interface and command-line tools that wrap and interoperate with programs including Phenix (software), REFMAC, Coot, ISOLDE, Flex-EM, Situs, MDFF, Rosetta (software suite), and ChimeraX. It implements map sharpening and local resolution estimation methods comparable to those in RELION and CryoSPARC, and includes validation metrics related to those used by MolProbity, EMRinger, Q-score, and MapQ. CCP-EM supports workflows for rigid-body docking with tools like UCSF Chimera, flexible fitting via Molecular dynamics, and real-space refinement akin to phenix.real_space_refine. It interoperates with visualization packages such as PyMOL, VMD (software), and Avogadro (software), and uses algorithms developed by groups at Max Planck Institute for Biophysical Chemistry, Howard Hughes Medical Institute, and National Center for Macromolecular Imaging.

Applications in Structural Biology

Researchers apply the suite to a wide range of macromolecular systems studied at facilities such as European Synchrotron Radiation Facility, National Synchrotron Light Source II, Argonne National Laboratory, and SLAC National Accelerator Laboratory. Use cases include reconstruction interpretation for complexes like the ribosome, ATP synthase, spliceosome, proteasome, ion channels, and viral capsids including studies of SARS-CoV-2 spike protein and other pathogens examined at Centers for Disease Control and Prevention. CCP-EM workflows facilitate integrative modeling that combines cryo-EM maps with data from X-ray crystallography, nuclear magnetic resonance spectroscopy, small-angle X-ray scattering, and mass spectrometry efforts at institutions like European Bioinformatics Institute and National Institute of Standards and Technology.

Validation and Performance

Validation tools in the suite reference community standards promulgated by Worldwide Protein Data Bank, International Union of Crystallography, and initiatives such as the Electron Microscopy Public Image Archive. Performance benchmarking has been carried out on hardware platforms ranging from local clusters at University of Cambridge to national HPC resources like ARCHER and XSEDE, and cloud providers utilized by groups at Google DeepMind and Amazon Web Services. Comparative studies juxtapose CCP-EM pipelines against standalone packages including RELION, CryoSPARC, Phenix (software), and Rosetta (software suite) using test sets from Electron Microscopy Data Bank and curated entries in the Protein Data Bank. Community-driven validation efforts have involved workshops with participants from European Molecular Biology Laboratory, MRC Laboratory of Molecular Biology, Wellcome Sanger Institute, Max Planck Society, and national facilities.

Licensing and Availability

The distribution model aligns with open-source practices adopted by projects like CCP4, Phenix (software), and EMAN2, with binaries and source code made available for academic institutions including University of York and commercial partners under terms compatible with reuse by researchers at Imperial College London and King's College London. Installers and containers are provided for platforms supported by Debian, Ubuntu, CentOS, and macOS package managers, and deployment recipes accommodate workflow managers such as Snakemake, Nextflow, and Common Workflow Language used in pipelines at European Grid Infrastructure and National Energy Research Scientific Computing Center. Collaboration and contributions are coordinated through repositories and issue trackers hosted by communities similar to those at GitHub and GitLab.

Category:Cryo-electron microscopy software