Apaper published in the journal Nucleic Acids Research presents a simplified DNA model called CGeNArate, which allows fast and accurate chromatin simulations and facilitates a detailed observation of structural modifications of the genome. The study has been led by Modesto Orozco, professor at the Faculty of Chemistry of the University of Barcelona (UB) and head of the Molecular Modelling and Bioinformatics Laboratory at the Institute for Research in Biomedicine (IRB Barcelona), located at the Barcelona Science Park.

DNA is the molecule that contains all the genetic information necessary for the development and functioning of living organisms. It is organized in a structure called “chromatin”, which is found inside the nucleus of cells. The shape that chromatin takes directly affects the activity of genes, and it is therefore important to have a detailed understanding of the structure of DNA and to be able to predict its variations.

Now, a team led by IRB Barcelona researcher and UB professor Modesto Orozco has developed a method which uses a specific approach that consists of simplifying a complex system by reducing its number of degrees of freedom and grouping atoms into coarse-graining units. In addition, it uses machine learning algorithms to reconstruct the atomic resolution of the simulated trajectories. This allows the structure and behaviour of DNA to be studied without the need for complex and time-consuming models, facilitating faster and more accessible research.

“This new model can be useful for projects that require studying the DNA’s structure in a detailed and agile way. Although the model is already functional, we are working to improve it and apply it into other components of the cell nucleus, which could open new opportunities in biomedical research”, notes Dr. Orozco, head of the Molecular Modelling and Bioinformatics laboratory at IRB Barcelona, and professor at the UB’s Department of Biochemistry and Molecular Biomedicine.

Detailed genomic information

The research team tested the new tool and validated its potential for obtaining high-speed chromatin simulations. The model allowed the observation of the behaviour of a specific section of DNA in a yeast gene, as well as modelling the structure of DNA in mitochondria and reproducing the flexibility of different ‘DNA structures in various contexts. “It was also able to simulate the formation of small circular DNA structures known as minicircles”, says David Farré-Gil, first author of the research and a PhD student in the same lab. These results demonstrate the effectiveness of the method for detailed analysis of DNA and chromatin.

The project was funded by the Spanish Ministry of Science, Innovation and Universities, the Agency for the Management of University and Research Grants (AGAUR), the Government of Catalonia and the European Union’s Research and Innovation Programme. The study has been carried out in collaboration with the University of Nottingham and has contributed to strengthening collaborations between European research institutions.

» Reference article: Farré-Gil, David; Arcon, Juan Pablo; Laughton, Charles A.; Orozco, Modesto. «CGeNArate: a sequence-dependent coarse-grained model of DNA for accurate atomistic MD simulations of kb-long duplexes». Nucleic Acids Research, maig de 2024.  DOI: 10.1093/nar/gkae444