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.
| 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 | University of York, Physics of Life Group |
| Organisation | University of York |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provide coarse-grained DNA modelling competence for studies on DNA supercoiling. |
| Collaborator Contribution | Our partners at the University of York, Dr Agnes Noy and Prof Mark Leake, provide expertise in atomistic DNA modelling and experimental methods. |
| Impact | This new collaboration is at an early stage and there are no concrete outputs as of March 2021 in form of publications. However, two BSc theses are currently in progress and these will be continued during MSc projects next year. The collaboration is multi-disciplinary and involves biophysics and the life sciences. |
| Start Year | 2019 |
| 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 "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 | 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 |