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.

Publications

10 25 50
 
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