oxDNA3 - Introducing Sequence-Specific Curvature And Elasticity Into A Coarse-Grained DNA Model
Lead Research Organisation:
University of Strathclyde
Department Name: Physics
Abstract
We propose to develop and apply the next-generation oxDNA3 coarse-grained model of DNA, featuring fundamentally important properties that are neglected in the current version oxDNA2.
oxDNA2 is the leading coarse-grained model of DNA, underpinning research into DNA bio- physics, materials science and nanotechnology in both academic and industrial contexts. It is the only CG model to date that combines the thermodynamics of DNA duplex formation with a good represen- tation of its average structural and mechanical properties in both single- and double-stranded DNA. However, it currently neglects sequence-dependent mechanical and structural properties, prohibiting its application to important open questions that underpin the role of DNA in living and engineered systems, including DNA-protein interactions.
To meet this challenge, we will leverage the combined expertise of the developers of the oxDNA2 model, specialists in high-performance computing, and experts in the sequence-dependence of DNA structure and mechanics. This synthesis puts us in a unique position to conduct this research. oxDNA3 will be released through both avenues, the popular LAMMPS molecular dynamics code and the oxDNA standalone code, accelerating its impact in both academia and biotechnology companies that are now using oxDNA.
oxDNA2 is the leading coarse-grained model of DNA, underpinning research into DNA bio- physics, materials science and nanotechnology in both academic and industrial contexts. It is the only CG model to date that combines the thermodynamics of DNA duplex formation with a good represen- tation of its average structural and mechanical properties in both single- and double-stranded DNA. However, it currently neglects sequence-dependent mechanical and structural properties, prohibiting its application to important open questions that underpin the role of DNA in living and engineered systems, including DNA-protein interactions.
To meet this challenge, we will leverage the combined expertise of the developers of the oxDNA2 model, specialists in high-performance computing, and experts in the sequence-dependence of DNA structure and mechanics. This synthesis puts us in a unique position to conduct this research. oxDNA3 will be released through both avenues, the popular LAMMPS molecular dynamics code and the oxDNA standalone code, accelerating its impact in both academia and biotechnology companies that are now using oxDNA.
Organisations
- University of Strathclyde (Lead Research Organisation)
- University of Oxford (Collaboration)
- Swiss Federal Institute of Technology in Lausanne (EPFL) (Collaboration)
- Imperial College London (Collaboration)
- University of York (Project Partner)
- Sandia National Laboratories (Project Partner)
- Ecole Polytechnique Fédérale de Lausanne (Project Partner)
- University of Leeds (Project Partner)
| Description | During the development of oxDNA3, we discovered a way how our coarse-grained RNA model could be improved and redesigned. The current RNA model has structural and mechanical shortcomings. We also gained insights into how DNA- and RNA-protein interactions could be modelled. |
| Exploitation Route | The developed models will be used by around 50 groups worldwide that use our coarse-grained models of nucleic acids. |
| Sectors | Agriculture Food and Drink Digital/Communication/Information Technologies (including Software) Energy Environment Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | The long term impacts of the project will form an important engineering tool for the rapidly growing bio-economy, including synthetic biology and bio-nanotechnology. These areas are key technologies for the delivery of the National Vision for Engineering Biology by the UK Government. |
| First Year Of Impact | 2025 |
| Sector | Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic |
| Title | Performance improvements of CG-DNA package in LAMMPS |
| Description | A 20% performance increase was achieved by refactoring force calculation routines. Unit tests have been added to ensure robustness of newly developed functionality. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The LAMMPS code is used by 1000s of researchers worldwide. The CG-DNA package is used by dozens of groups. |
| URL | https://www.lammps.org |
| Description | oxDNA Developer Network |
| Organisation | Imperial College London |
| Department | Department of Bioengineering |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This collaboration works towards the next generation of oxDNA model, which will include sequence-specific curvature and elasticity. I am coordinating these activities, lead the development and am responsible for implementations into the LAMMPS code. |
| Collaborator Contribution | Prof John H. Maddocks seconds a PhD student. |
| Impact | We are currently in the process of applying for funding. The collaboration involves the disciplines of applied mathematics, (bio-)physics, (bio-)chemistry and includes aspects of research software engineering. |
| Start Year | 2020 |
| Description | oxDNA Developer Network |
| Organisation | Swiss Federal Institute of Technology in Lausanne (EPFL) |
| Country | Switzerland |
| Sector | Public |
| PI Contribution | This collaboration works towards the next generation of oxDNA model, which will include sequence-specific curvature and elasticity. I am coordinating these activities, lead the development and am responsible for implementations into the LAMMPS code. |
| Collaborator Contribution | Prof John H. Maddocks seconds a PhD student. |
| Impact | We are currently in the process of applying for funding. The collaboration involves the disciplines of applied mathematics, (bio-)physics, (bio-)chemistry and includes aspects of research software engineering. |
| Start Year | 2020 |
| Description | oxDNA Developer Network |
| Organisation | University of Oxford |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This collaboration works towards the next generation of oxDNA model, which will include sequence-specific curvature and elasticity. I am coordinating these activities, lead the development and am responsible for implementations into the LAMMPS code. |
| Collaborator Contribution | Prof John H. Maddocks seconds a PhD student. |
| Impact | We are currently in the process of applying for funding. The collaboration involves the disciplines of applied mathematics, (bio-)physics, (bio-)chemistry and includes aspects of research software engineering. |
| Start Year | 2020 |
| Description | oxDNA Developer Network |
| Organisation | University of Oxford |
| Department | Department of Physics |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This collaboration works towards the next generation of oxDNA model, which will include sequence-specific curvature and elasticity. I am coordinating these activities, lead the development and am responsible for implementations into the LAMMPS code. |
| Collaborator Contribution | Prof John H. Maddocks seconds a PhD student. |
| Impact | We are currently in the process of applying for funding. The collaboration involves the disciplines of applied mathematics, (bio-)physics, (bio-)chemistry and includes aspects of research software engineering. |
| Start Year | 2020 |
| Title | LAMMPS CG-DNA package |
| Description | A simulation package for coarse-grained simulation of DNA and RNA |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | The LAMMPS code is used by 1000s of researchers. The CG-DNA package is used in dozens of groups worldwide. |
| URL | https://www.lammps.org |
| Description | CECAM Workshop "Biomolecular Simulations at the Mesoscale", Trento, Italy |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | This workshop brought together international experts in coarse-grained simulation methods and biomolecular modelling. The objectives were to explore the technical basis of mesoscale modelling and to discuss existing challenges on the mesoscale in the framework of the integrative modelling of biological systems. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.cecam.org/workshop-details/biomolecular-simulations-at-the-mesoscale-1330 |
| Description | CECAM Workshop "Multiscale simulations of DNA from electrons to nucleosomes: 22 years of the Ascona B-DNA Consortium" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The Ascona B-DNA Consortium started a new initiative with the aim to examine the sequence-dependent mechanical properties at the hexanucleotide level and the proposed meeting should be an opportunity to discuss the results of these very large-scale simulations and collaborative effort. |
| Year(s) Of Engagement Activity | 2023 |
| Description | CamRAREfest24 by the CamRARE Cambridge Rare Disease Network |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Around 800 participant attended the event, where we had a stand with DNA and RNA models, a poster and ran interactive DNA simulations |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.camraredisease.org/rarefest24/ |
| Description | Higgs Centre for Theoretical Physics Workshop 'DNA Supercoiling', Santadi, Sardinia, Italy |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | 25 researchers attended this international workshop on DNA supercoiling, statistical physics, theoretical models and experiments. |
| Year(s) Of Engagement Activity | 2023 |
| Description | oxDNA User and Developer Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The workshop serves to coordinate, strengthen and inform the global community of oxDNA users and developers. A direct outcome was the expressed desire to focus the model development on RNA nanotechnology and DNA- and RNA-protein interactions. |
| Year(s) Of Engagement Activity | 2024 |