The Protein Circular Dichroism Data Bank, the DichroWeb Server, and ValiDichro: Data Sharing, Analysis and Standards Resources for CD Spectroscopy
Lead Research Organisation:
Queen Mary University of London
Department Name: Sch of Biological and Chemical Sciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Circular Dichroism (CD) spectroscopy is used in structural biology for determining protein secondary structure, detecting conformational changes, and examining macromolecular interactions and protein folding, and is a method designated by regulatory agencies for the characterisation of pharmaceutical proteins for human use.
This proposal is to enhance, curate and operate a comprehensive set of electronic archiving and analysis resources for CD spectroscopy.
It includes the Protein Circular Dichroism Data Bank (PCDDB), a deposition, searchable and downloadable data bank of CD spectra, which began operation earlier this year. The aim of the data bank is to provide public archiving facilities and open access to validated circular dichroism spectral and metadata. The project would support continuing development, enhanced functionalities and modifications based on our experience gained in operating it and user feedback, as well as enabling it to be run as an ongoing user resource. The project also includes enhancements to, and operation of, DichroWeb, a widely-used online server for the analysis of circular dichroism data.
This proposal includes the development of a suite of support tools for novel types of CD analyses based on data deposited in the data bank, including spectral nearest neighbour identification, spectral matching (with applications in bioprocessing), and back calculations of spectra from crystallographic coordinates. It will also include enhanced validation software (establishing standards for spectroscopic data and ensuring the data quality in the PCDDB). A further development will be a one-stop-shop CDpipeline server that will incorporate processing, display, analyses, validation and deposition (aiding casual users of the method as well as improving throughput for more advanced users).
Together these bioinformatics resources will provide enabling and supportive tools in CD spectroscopy for the structural biology and bioinformatics communities.
This proposal is to enhance, curate and operate a comprehensive set of electronic archiving and analysis resources for CD spectroscopy.
It includes the Protein Circular Dichroism Data Bank (PCDDB), a deposition, searchable and downloadable data bank of CD spectra, which began operation earlier this year. The aim of the data bank is to provide public archiving facilities and open access to validated circular dichroism spectral and metadata. The project would support continuing development, enhanced functionalities and modifications based on our experience gained in operating it and user feedback, as well as enabling it to be run as an ongoing user resource. The project also includes enhancements to, and operation of, DichroWeb, a widely-used online server for the analysis of circular dichroism data.
This proposal includes the development of a suite of support tools for novel types of CD analyses based on data deposited in the data bank, including spectral nearest neighbour identification, spectral matching (with applications in bioprocessing), and back calculations of spectra from crystallographic coordinates. It will also include enhanced validation software (establishing standards for spectroscopic data and ensuring the data quality in the PCDDB). A further development will be a one-stop-shop CDpipeline server that will incorporate processing, display, analyses, validation and deposition (aiding casual users of the method as well as improving throughput for more advanced users).
Together these bioinformatics resources will provide enabling and supportive tools in CD spectroscopy for the structural biology and bioinformatics communities.
Planned Impact
Circular dichroism (CD) spectroscopy is a widely used technique in structural biology. The resources proposed would benefit those who utilise CD in both academia and the commercial sector.
Because CD is a spectroscopic technique currently meeting ICH Guidelines for characterisation of pharmaceuticals for human use, there has already been significant interest in the tools described in this proposal expressed by the pharmaceutical industry, SMEs and regulatory agencies such as the European Medicines Agency and the US Food and Drug Administration. The Protein Circular Dichroism Data Bank archive will be a resource for well-characterised protein spectra and can be a traceable resource for documentation of medicinal proteins (for bioprocessing and biosimilars comparisons). The validation tools and spectral comparisons and metrics tools to be developed will have value in protein characterisations and quality evaluations, and DichroWeb has already proven to be a useful tool by big pharma, SME and food industry users.
Because CD is a spectroscopic technique currently meeting ICH Guidelines for characterisation of pharmaceuticals for human use, there has already been significant interest in the tools described in this proposal expressed by the pharmaceutical industry, SMEs and regulatory agencies such as the European Medicines Agency and the US Food and Drug Administration. The Protein Circular Dichroism Data Bank archive will be a resource for well-characterised protein spectra and can be a traceable resource for documentation of medicinal proteins (for bioprocessing and biosimilars comparisons). The validation tools and spectral comparisons and metrics tools to be developed will have value in protein characterisations and quality evaluations, and DichroWeb has already proven to be a useful tool by big pharma, SME and food industry users.
People |
ORCID iD |
| Robert Janes (Principal Investigator) |
Publications
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
Drew ED
(2020)
PDBMD2CD: providing predicted protein circular dichroism spectra from multiple molecular dynamics-generated protein structures.
in Nucleic acids research
Janes RW
(2017)
PDB2CD visualises dynamics within protein structures.
in European biophysics journal : EBJ
Mavridis L
(2017)
PDB2CD: a web-based application for the generation of circular dichroism spectra from protein atomic coordinates.
in Bioinformatics (Oxford, England)
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
Sarma G
(2017)
Collision energy dependence of state-to-state differential cross sections for rotationally inelastic scattering of H2O by He.
in Physical chemistry chemical physics : PCCP
Wallace Bonnie A.
(2020)
Tools and Resources for Circular Dichroism Spectroscopy
in BIOPHYSICAL JOURNAL
Whitmore L
(2017)
PCDDB: new developments at the Protein Circular Dichroism Data Bank.
in Nucleic acids research
| Description | The work undertaken in, and supported by this grant has developed tools and resources that have been utilised by many researchers to support their studies. Additionally, the availability of the data resource within this grant has enabled others to develop further supportive tools to the scientific community. |
| Exploitation Route | The tools and resource generated from this grant will continue to enable researchers to have the availability of data to act as supportive/complementary information for their studies. They may well become the main focus of their work in development of further tools to support and assist the scientific community. |
| Sectors | Agriculture, Food and Drink,Education,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 | 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 |
| 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 | Dichromatch |
| Description | Presents four different ways of evaluating the closest matching (three in each case) Circular Dichroism spectra in a given Reference set of spectra (default are those in the Protein Circular Dichroism Data Bank). |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | At this time I am not aware of "notable impacts" that have arisen specifically from this tool however it is well used by researchers. |
| URL | http://dichromatch.cryst.bbk.ac.uk/ |
| Title | PDB2CD |
| Description | PDB2CD is a research tool that enables scientists to generate Circular Dichroism spectra from the atomic structure coordinates of proteins. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Since its publication it has been accessd by over 150 users in 34 countries so far. |
| URL | http://pdb2cd.cryst.bbk.ac.uk |
| 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 | PDB2CD |
| Description | Utilising data from the atomic structure of a protein to generate a Circular Dichroism Spectrum for that protein. |
| Type Of Technology | Webtool/Application |
| Year Produced | 2017 |
| Impact | Since its publication it has been accessd by over 150 users in 34 countries so far. |
| URL | http://pdb2cd.cryst.bbk.ac.uk |
| 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 | Beamline Panel |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Our evaluations of the Beamlines lead to changes/additions that enhanced the facilities Funding for the ANKA facility was ultimately gained |
| Year(s) Of Engagement Activity | 2013 |
| Description | Brazil - SRCD Meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a meeting aimed at promoting Synchrotron Radiation Circular Dichroism Spectroscopy to researchers and their group members in Brazil. It generated a lot of interest in the possibility of developing a beamline on the Brazillian Synchrotron at Campinas, where the meeting was held. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://pages.cnpem.br/srcd2015/ |
| Description | Brazil-Int-Exch |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was an intitiation meeting for collaborations with Brazil. Guests included the Brazillian Ambassador, the Brazillian Science Attache, the UK Head of Science Without Borders and BBSRC staff were also in attendance. This meeting generated a lot of enthusiasm for collaborative projects centred around circular dichroism and synchrotron radiation circular dichroism spectroscopy and has become the progenitor for a formal application being made for the creation of an SRCD beamline on the Brazillian Synchrotron at Campinas. |
| Year(s) Of Engagement Activity | 2013 |
| 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 | ECCB 2014 Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I organised this workshop which was selected to be part of the 13th European Conference on Computational Biology. This was entitled as a "Workshop on Informatics Based Approaches for Circular Dichroism Data", and was specifically aimed at widening the audience interest in CD and particularly those with a computational bias aiming to stimulating their interest in the field. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Eu/UK CD/SRCD Workshop (Now part of the Warwick Analytical Sciences Workshop) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Numerous attendees have now become regular users of Circular Dichroism and Synchrotron Radiation Circular Dichroism as a result of the training they have received Some short-term collaborative projects have been instigated as a result of these workshops |
| Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016 |
| URL | http://www2.warwick.ac.uk/fac/sci/wcas/events/analytical_sciences_summer_school_winter_workshop/ |
| Description | Frontiers in SRCD |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was the 3rd in a series of meetings (1st - 2001, 2nd - 2009) aimed at presenting Sychrotron Radiation Circular DIchroism spectroscopy to a wider scientific audience; those practicing the technique and those interested in using it. Many members of the audience came away with a more enlightened view of what the technique could do for their research. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.ibg.kit.edu/nmr/673.php |
| Description | Frontiers in SRCD (2) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a talk given by the Postdoc on the grant. |
| Year(s) Of Engagement Activity | 2015 |
| 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 | Open Days (QM) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | Primarily science presentations at Open Days at QM and this did indeed spark questions and interest from those that assembled to watch the demonstrations I have no direct knowledge of impact from my presentations, but interest in studying in our School at QM has been rising steadily recently (but I cannot attribute this to my involvement!!) |
| Year(s) Of Engagement Activity | 2008,2009,2010,2011,2012,2013,2014 |
| Description | Shanghai Meeting |
| 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 the 1st Shanghai Symposium of Membrane Active Peptides and Proteins and the aims were to develop interests in research areas involving synchrotron radiation circular dichroism spectroscopy |
| Year(s) Of Engagement Activity | 2015 |
| Description | Workshop - Sao Paolo - Brazil |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | These were Workshops run in Sao Paolo, Brazil, designed to introduce those in the audience to the techniques of Circular Dichroism and Sychrotron Radiation Circular Dichroism Spectroscopy and all aspects associated with these techniques. This included both from a theoretical background, experimental methodologies, and practical aspects of interpretation of the results obtained from these techniques. While the 2016 Workshop was CD/SRCD directed as a topic the 2017 Workshop incorporated other techniques being a part of the São Paulo School of Advanced Science on Biophysical Methods to Study Biomolecular Interactions. |
| Year(s) Of Engagement Activity | 2016,2017 |
| URL | http://espca.fapesp.br/school/sao_paulo_school_of_advanced_science_on_biophysical_methods_to_study_b... |
| Description | Workshop Brazil One |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Circular Dichroism/Synchrotron Radiation Circular Dichroism Spectroscopy Workshop training for those wishing to gain knowledge of the technique and how to use it effectively |
| Year(s) Of Engagement Activity | 2014 |
| Description | Workshop Brazil Two |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Circular Dichroism/Synchrotron Radiation Circular Dichroism Spectroscopy Workshop training for those wishing to gain knowledge of the technique and how to use it effectively. So successful was the first workshop that a second one was run in another part of the country to attract a further audience of users. Additionally, some of those trained in the previous workshop have now become users of Synchrotron CD beamlines worldwide. |
| Year(s) Of Engagement Activity | 2015 |