Bioinformatics Resources for Circular Dichroism Spectroscopy and Structural Biology: Operation, Enhancement, Curation, and New Developments
Lead Research Organisation:
Queen Mary University of London
Department Name: Sch of Biological & Behavioural Sciences
Abstract
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Technical Summary
Circular Dichroism (CD) spectroscopy is a technique that is widely used in biochemistry, structural biology, and biophysics for determining protein secondary structures, detecting conformational changes, and examining macromolecular interactions and protein folding, and is a method designated by international regulatory agencies for characterisation of pharmaceutical proteins.
This proposal is to operate, maintain, curate, and enhance a comprehensive set of electronic archiving and analysis resources for CD spectroscopy. It is a renewal/follow-on application for a BBR grant that enabled creation and development of bioinformatics resources for data-sharing and analysis of CD spectroscopic data, and for inter-operability tools relating CD spectroscopy, crystallography and NMR spectroscopy.
It includes the Protein Circular Dichroism Data Bank (PCDDB), a deposition, searchable and downloadable data bank of CD spectra which provides public archiving facilities and open access to validated CD spectral and meta-data, DichroWeb, the most widely-used online server for the analysis of CD data; the CDTools data processing, analysis and display software; 2Struc, for secondary structure calculations and displays based on coordinate data from crystallography and NMR; PDB2CD for calculating CD spectra based on 3D structures; and DichroMatch, for identifying close spectral neighbours for use in structural and functional studies. New developments will include enhancements to all of these, and new tools such as an online pipeline facility to simplify data processing, validation, analysis, display, and data-sharing (aiding casual users as well as improving throughput for more advanced users), tools for quantitative spectral comparisons (with applications in bioprocessing), and for analyses of oriented CD spectra. Finally, it will include extensive user liaison and training facilities, and outreach in the area of data-sharing.
This proposal is to operate, maintain, curate, and enhance a comprehensive set of electronic archiving and analysis resources for CD spectroscopy. It is a renewal/follow-on application for a BBR grant that enabled creation and development of bioinformatics resources for data-sharing and analysis of CD spectroscopic data, and for inter-operability tools relating CD spectroscopy, crystallography and NMR spectroscopy.
It includes the Protein Circular Dichroism Data Bank (PCDDB), a deposition, searchable and downloadable data bank of CD spectra which provides public archiving facilities and open access to validated CD spectral and meta-data, DichroWeb, the most widely-used online server for the analysis of CD data; the CDTools data processing, analysis and display software; 2Struc, for secondary structure calculations and displays based on coordinate data from crystallography and NMR; PDB2CD for calculating CD spectra based on 3D structures; and DichroMatch, for identifying close spectral neighbours for use in structural and functional studies. New developments will include enhancements to all of these, and new tools such as an online pipeline facility to simplify data processing, validation, analysis, display, and data-sharing (aiding casual users as well as improving throughput for more advanced users), tools for quantitative spectral comparisons (with applications in bioprocessing), and for analyses of oriented CD spectra. Finally, it will include extensive user liaison and training facilities, and outreach in the area of data-sharing.
Planned Impact
Circular dichroism (CD) spectroscopy is a widely-used technique in biochemistry and structural biology, for studying protein structures, folding, and conformational changes associated with different conditions, environmental effects, and drug binding. This proposal is for renewal of an existing BBR grant to enable future provision, operation, maintenance, enhancement, and development of a series of existing and new tools and resources for data-sharing and analyses of CD spectral data. The widely-used resources described in this proposal will continue to benefit a broad base of scientists who utilise CD spectroscopy in both academia and the commercial sector, and new tools will be developed to extract and utilise additional information from CD data.
CD spectroscopy is a method that is regularly used in academia to characterise proteins and other biomacromolecules, often in conjunction with methods such as crystallography and NMR spectroscopy. It is also a spectroscopic technique which meets ICH (International Council for Harmonisation of Technical Requirements) for characterisation of pharmaceuticals for human use, so there has also been significant interest by the pharmaceutical industry in the tools described in this proposal.
The Protein Circular Dichroism Data Bank (PCDDB) has already become a well-used resource for protein spectra and metadata and is a traceable resource for documentation of medicinal proteins (for bioprocessing and biosimilars comparisons), a means of fulfilling research council and publication requirements for data-sharing, and provides a freely-available means for re-use and re-purposing of existing data. The analysis, validation, spectral comparison and other tools to be enhanced, augmented and developed in this project will have value in protein characterisations and quality evaluations, and thereby support and enhance research in the wider science base.
The long-established DichroWeb analysis server [which was cited as an early example of impact in the RCUK "Study on the Economic Impact of the Research Councils"], is continually updated and enhanced, and has a proven record of widespread use in academia and by big pharma, SMEs and the food industry. This and our other existing resources have also proven to be valuable teaching tools in undergraduate and postgraduate programmes, and the user liaison, media, and training activities provide unique resources to the scientific community, thereby enhancing the skills base of the UK.
It is thus expected that the resources in this project will continue to provide means of characterising, sharing and enhancing the utility of existing data, and provide new means of quality control and novel analyses for future characterisations of proteins and other biomacromolecules by both the academic and commercial sectors.
CD spectroscopy is a method that is regularly used in academia to characterise proteins and other biomacromolecules, often in conjunction with methods such as crystallography and NMR spectroscopy. It is also a spectroscopic technique which meets ICH (International Council for Harmonisation of Technical Requirements) for characterisation of pharmaceuticals for human use, so there has also been significant interest by the pharmaceutical industry in the tools described in this proposal.
The Protein Circular Dichroism Data Bank (PCDDB) has already become a well-used resource for protein spectra and metadata and is a traceable resource for documentation of medicinal proteins (for bioprocessing and biosimilars comparisons), a means of fulfilling research council and publication requirements for data-sharing, and provides a freely-available means for re-use and re-purposing of existing data. The analysis, validation, spectral comparison and other tools to be enhanced, augmented and developed in this project will have value in protein characterisations and quality evaluations, and thereby support and enhance research in the wider science base.
The long-established DichroWeb analysis server [which was cited as an early example of impact in the RCUK "Study on the Economic Impact of the Research Councils"], is continually updated and enhanced, and has a proven record of widespread use in academia and by big pharma, SMEs and the food industry. This and our other existing resources have also proven to be valuable teaching tools in undergraduate and postgraduate programmes, and the user liaison, media, and training activities provide unique resources to the scientific community, thereby enhancing the skills base of the UK.
It is thus expected that the resources in this project will continue to provide means of characterising, sharing and enhancing the utility of existing data, and provide new means of quality control and novel analyses for future characterisations of proteins and other biomacromolecules by both the academic and commercial sectors.
People |
ORCID iD |
Robert Janes (Principal Investigator) |
Publications
Wallace Bonnie A.
(2020)
Tools and Resources for Circular Dichroism Spectroscopy
in BIOPHYSICAL JOURNAL
Wallace B
(2023)
The PCDDB project: Tools and resources for CD analyses, archiving, display, and sharing
in Biophysical Journal
Drew ED
(2020)
Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity.
in BMC molecular and cell biology
Miles AJ
(2021)
Tools and methods for circular dichroism spectroscopy of proteins: a tutorial review.
in Chemical Society reviews
Ramalli SG
(2022)
The PCDDB (Protein Circular Dichroism Data Bank): A Bioinformatics Resource for Protein Characterisations and Methods Development.
in Journal of molecular biology
Drew ED
(2020)
PDBMD2CD: providing predicted protein circular dichroism spectra from multiple molecular dynamics-generated protein structures.
in Nucleic acids research
Janes RW
(2023)
DichroPipeline: A suite of online and downloadable tools and resources for protein circular dichroism spectroscopic data analyses, interpretations, and their interoperability with other bioinformatics tools and resources.
in Protein science : a publication of the Protein Society
Whitmore L
(2018)
DichroMatch at the protein circular dichroism data bank (DM@PCDDB): A web-based tool for identifying protein nearest neighbors using circular dichroism spectroscopy.
in Protein science : a publication of the Protein Society
Description | This grant is generating bioinformatics tools to support the scientific community that engage in research using circular dichroism spectroscopy and other related techniques, to make analyses of results easier to accomplish |
Exploitation Route | Our bioinformatics tools enable those engaged in research to analyse their data using very user-friendly packages. This greatly increases their output and their ability to interpret their results which in turn means answers to many important science questions can be gained in a fast and efficient way. One area is to use our tools to compare experimentally obtained CD spectra with other such spectra held it the Protein Circular Dichroism Data Bank (PCDDB) to establish the extent of similarity to spectra in this resource. In so doing this can often lead to an understanding of the possible structure of the proteins being examined; invaluable information in many scientific fields. Our most recent tool enables a fast and effective graphical examination of comparisons between two protein structures (2StrucCompare) which is proving to be a popular tool. |
Sectors | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
Description | Biotechnology and Biological Sciences Research Council (BBSRC) |
Amount | £450,573 (GBP) |
Funding ID | BB/J019194/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2013 |
End | 06/2018 |
Description | Biotechnology and Biological Sciences Research Council (BBSRC) Tools and Resources |
Amount | £118,022 (GBP) |
Funding ID | BB/I023887/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2011 |
End | 04/2013 |
Description | CALIPSOplus |
Amount | £2,000 (GBP) |
Organisation | Helmholtz Association of German Research Centres |
Department | Helmholtz-Zentrum Dresden-Rossendorf |
Sector | Academic/University |
Country | Germany |
Start | 05/2017 |
End | 04/2021 |
Description | Collaborative Sino-UK SRCD Spectroscopy Studies |
Amount | £24,800 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2004 |
End | 03/2012 |
Description | FP7 Infrastructure Programme CALIPSO |
Amount | £10,000 (GBP) |
Funding ID | 312284 |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 06/2012 |
End | 05/2015 |
Description | IUPAC |
Amount | $9,600 (USD) |
Funding ID | 2010-033-2-024 |
Organisation | International Union of Pure and Applied Chemistry (IUPAC) |
Sector | Charity/Non Profit |
Country | United States |
Start | 06/2010 |
End | 05/2014 |
Title | 2StrucCompare |
Description | Graphical User Interface designed to enable a simple investigation into the similarities and differences between two protein structures |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Since its inception there are now over 360 users who have performed 580 sessions on this package. |
URL | https://2struccompare.cryst.bbk.ac.uk/index.php |
Title | PDBMD2CD |
Description | This research tool enables the predictions of CD spectra from atomic resolution structures. This is a multi-entry package designed to support, for example, those that generate clusters of structures from Molecular Dynamics Simulations to enable comparison of the spectra that are generated with experimentally determined spectra as a support for validaton and interpretation of their results. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Although the tool has only recently become available, since the beginning of the year over 270 new users have used from 34 countries. |
URL | https://pdbmd2cd.cryst.bbk.ac.uk/ |
Title | PCDDB |
Description | The Protein Circular Dichroism Data Bank (PCDDB) - offering a repository for CD and Synchrotron Radiation Circular Dichroism (SRCD) spectra and meta data (including experimental/sample data and machine parameters) providing a resource for the science community. This is an ongoing resource being continuously enhanced and enriched by us to provide a secure site for the deposition of CD(SRCD) spectral data and associated meta-data for archiving purposes. This also enables the scientific community to access this data in support of their own research. |
Type Of Material | Database/Collection of data |
Year Produced | 2010 |
Provided To Others? | Yes |
Impact | Currently well over 500,000 entry downloads by the science community and gaining swiftly in citations |
URL | http://pcddb.cryst.bbk.ac.uk/home.php |
Description | Bonnie A Wallace |
Organisation | Birkbeck, University of London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a linked grant where both parties collaborate mutually on many aspects of the work. Our primary directive is creating tools for the resource of various kinds. We jointly contribute in all aspects of the grant. |
Collaborator Contribution | This is a linked grant where both parties collaborate on many aspects of the work. My collaborator's group is primarily responsible for the maintainance and expansion of the resource and supporting processing website facilities. We jointly contribute in all aspects of the grant. |
Impact | All of these are multi-disciplinary by the nature of the technique of CD which lends itself to utilisation in many disparate fields of study, and to bioinformatics where the tools can be used as a basis for analysing the content for many reasons (which we are doing ourselves as well) The Protein Circular Dichroism Data Bank website Dichromatch server ValiDichro server Publications Tools to support the resource |
Description | Paul Anderson |
Organisation | Queen Mary University of London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Spectroscopic studies |
Collaborator Contribution | Provided samples |
Impact | Talks at international meetings Papers in preparation |
Start Year | 2011 |
Description | Robin Maytum |
Organisation | University of Bedfordshire |
Department | Department of Life Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Spectroscopic studies |
Collaborator Contribution | Sample provision |
Impact | We are actively studying tropomyosin, mutations in which are associated with the disease Familial Hypertrophic Cardiomyopathy (FHC). An abstract has been published to date Talks at international meetings Papers are in preparation |
Start Year | 2009 |
Title | 2StrucCompare |
Description | Graphical User Interface designed to enable a simple investigation into the similarities and differences between two protein structures |
Type Of Technology | Webtool/Application |
Year Produced | 2019 |
Impact | Since its inception there are now over 360 users who have performed 580 sessions on this package. |
Title | PDBMD2CD |
Description | This is a webtool for creating CD spectra from multiple protein atomic structure files. Its main use is for researchers who generate multiple structures (from techniques such as Molecular Dynamics Simulations) where the aim is to compare the generated spectra with those obtained experimentally. |
Type Of Technology | Webtool/Application |
Year Produced | 2020 |
Impact | Although not long in existance, since the beginning of the year over 270 new users from 34 countries have used this package. |
URL | https://pdbmd2cd.cryst.bbk.ac.uk/ |
Description | Centre for Computational Biology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | This was an invited talk for the Centre for Computational Biology entitled: "Bioinformatics tools linking Protein Crystallography and Circular Dichroism Spectroscopy". This was to an audience with knowledge of CD and of Crystallography but who were periphery to main stream scientists in these areas of science. The aims of the talk were to introduce them to the appreciation of how CD and Crystallography can be used to provide complimentary information about protein structure which could be beneficial to their own research. |
Year(s) Of Engagement Activity | 2018 |
Description | Flu viruses: How can rational drug design help? |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | This was a talk in the "UCL Science Centre Lecture" series aimed at the General Public and Schools (6th Form Colleges) to increase knowledge of science subjects. This might have been the first talk to incorporate information on "Covid-19" and its' mechanism of action given in the UK. |
Year(s) Of Engagement Activity | 2020 |
Description | IUBMB/IUPAB Advanced School and Workshop Cuba |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | This was the "IUBMB/IUPAB Advanced School and Workshop, Protein-protein and protein-membrane interaction: experimental and theoretical approaches", a workshop in Cuba with an International audience of around 60 participants. Our aims (Prof. B.A. Wallace was also present) were to school them in the background theory, good practices, processing, and interpretation of Circular Dichroism Spectroscopy. My primary role was to provide a practical computer lab class with them on processing and analysing CD data, together with introducing them to related bioinformatics tools associated with CD (that we have developed). The audience was very responsive in asking questions which meant that they benefited a lot from the interactions during this class. |
Year(s) Of Engagement Activity | 2018 |
URL | http://karin.fq.uh.cu/~valiente/advanced_school_varadero_2018/ |
Description | Tools and Resources Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | This was an invited talk on the Tools and Resources available from the PCDDB. The aims were to enlighten the audience as to what was available to them to utilise. As a result at least two of the tools are now being used in the Department of Pharmaceutical Sciences in the University of Vienna to support their research analyses. |
Year(s) Of Engagement Activity | 2022 |
Description | Tools and Resources Talk for a new SRCD beamline in Brazil |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | This was an invited talk given online as part of the 2nd Brazilian Workshop on Synchrotron Radiation Circular Dichroism (CEDRO workshop) held in June 2022. The aims were to illustrate the available tools and resources produced by the PCDDB group to support and facilitate research data processing and analyses. As a result many of these tools will be available at the new SRCD beamline facility in Brazil. |
Year(s) Of Engagement Activity | 2022 |
URL | https://pages.cnpem.br/cedroworkshop/ |