Studying how chromatin changes requires capturing molecular movements and interactions that are difficult to resolve experimentally. Now, an international research team led by IRB Barcelona, the University of Cambridge, UT Southwestern Medical Center and the Howard Hughes Medical Institute has developed OpenCGChromatin, a tool that functions as a computational microscope, using simulations to explore how chromatin folds, how its components interact, and what forces hold its structures together.
“The challenge is to connect interactions between individual molecules with the behavior of much larger stretches of chromatin. This tool allows us to study both within the same framework and understand how small molecular changes can alter DNA packaging,” says Modesto Orozco, corresponding author on the study published in Nature Communications.
The tool combines a detailed representation of DNA and proteins with greater computational efficiency, allowing researchers to study chromatin systems more than ten times larger than those accessible to previous models with comparable resolution, including assemblies containing hundreds of nucleosomes. Its simulations reproduce observations from microscopy and biochemical experiments while also revealing movements of flexible histone regions that are difficult to resolve experimentally.
“What Kieran Russell, first author of this study, has achieved is remarkable. He has pushed the state of the art in chromatin modeling, allowing us to simulate systems at a scale and level of molecular detail that were previously out of reach. We can now connect the chemical makeup of chromatin to its organization across scales—from molecular interactions to gene-sized structures and biomolecular condensates—while remaining closely grounded in experiment. I am very excited because OpenCGChromatin opens up a completely new range of questions that we can now address computationally,” says Rosana Collepardo-Guevara e, who also co-led the study.
“The simulations help us understand why changing the spacing between nucleosomes, or adding chemical modifications to histones, can make chromatin behave differently,” adds David Farré-Gil, also an author of the paper.
OpenCGChromatin is available as open-source software, allowing other researchers to use it to investigate the physical principles underlying genome organization.
“The challenge is to connect interactions between individual molecules with the behavior of much larger stretches of chromatin. This tool allows us to study both within the same framework and understand how small molecular changes can alter DNA packaging,” says Modesto Orozco, corresponding author on the study published in Nature Communications.
The tool combines a detailed representation of DNA and proteins with greater computational efficiency, allowing researchers to study chromatin systems more than ten times larger than those accessible to previous models with comparable resolution, including assemblies containing hundreds of nucleosomes. Its simulations reproduce observations from microscopy and biochemical experiments while also revealing movements of flexible histone regions that are difficult to resolve experimentally.
“What Kieran Russell, first author of this study, has achieved is remarkable. He has pushed the state of the art in chromatin modeling, allowing us to simulate systems at a scale and level of molecular detail that were previously out of reach. We can now connect the chemical makeup of chromatin to its organization across scales—from molecular interactions to gene-sized structures and biomolecular condensates—while remaining closely grounded in experiment. I am very excited because OpenCGChromatin opens up a completely new range of questions that we can now address computationally,” says Rosana Collepardo-Guevara e, who also co-led the study.
“The simulations help us understand why changing the spacing between nucleosomes, or adding chemical modifications to histones, can make chromatin behave differently,” adds David Farré-Gil, also an author of the paper.
OpenCGChromatin is available as open-source software, allowing other researchers to use it to investigate the physical principles underlying genome organization.