emDNA – A Tool for Modeling Protein-decorated DNA Loops and Minicircles at the Base-pair Step Level


Understanding nucleic acid structure provides essential insight into functional roles fundamental to molecular biology. Unfortunately, experimentally determining DNA structure at high resolution is tedious, expensive and not always tractable, particularly for large complex systems, which can show significant molecular flexibility. There has been extensive research into developing computational tools for modeling and manipulating nucleic acid structure as a complementary approach to study nucleic acid structure in silico. It is well known from biophysical studies how proteins and other molecules interact with double-helical DNA in its immediate context, but less is known about the larger-scale structural interactions that occur in protein-decorated loops and minicircles. Indeed, minicircle DNAs are novel non-viral DNA vectors that have become promising options for gene therapy, DNA vaccines, or intermediates in cell-based therapies. Current computer models of DNA range from coarse-grained simulations that forgo fine-grained physical and chemical information to tackle larger-scale systems to precise all-atom molecular dynamics investigations that yield time and spatially dependent portrayals of small DNA fragments.

In a new study published in the Journal of Molecular Biology, investigators Robert Young, Nicolas Clauvelin and led by Professor Wilma Olson at Rutgers University developed a new tool for generating optimized structures of DNA at thermal equilibrium with built-in or user-generated elastic models. This new tool is called emDNA, a command-line software application that enables users to create spatially constrained, energy-optimized DNA models. The new tool enables users of any ability level to create and explore mesoscale models of their own design in conjunction with the case studies presented in the article. Applications of emDNA to a well-characterized minicircle with distinctive sequence-dependent properties were highlighted in the reported case studies. The emDNA software is available to the general public on GitHub (https://nicocvn.github.io/emDNA/).

In this case, treating DNA at the base-pair level with rigid-body characteristics makes it possible to create models with hundreds of base pairs of length from small, sequence-specific features discovered via experimentation. This framework is utilized by the emDNA software to create optimal DNA structures at thermal equilibrium with pre-built or user-generated elastic models. Researchers now have a new method for studying DNA functionality thanks to the emDNA program. During the energy minimization of polymeric structures, users can regulate the chain length, sequence composition, location of the fragment ends, and range of local structural deformations. The companion tool, emDNA_probind, offers the capability to optimize DNA structures containing one or more bound proteins through a dedicated minimization procedure. These emDNA features provide helpful insights into how local regions of interest interact with the overall structure of the DNA, such as how tailored ligands may modify looping propensities and related genetic activity. The overall DNA configuration can be changed by selecting intrinsic features at the base-pair step level. Although emDNA was designed to be user-friendly, there are some limitations to consider. Depending on the size of the DNA fragment and the quantity of ramped models, the optimization and protein-decoration ramping procedures may require higher computing resources.

For example, optimizing a 100-bp design may take less than two minutes, In contrast a 1000-bp configuration may take days, depending on the computational resources available. This can be a concern when utilizing the emDNA_probind tool since the uptake of certain proteins involves a considerable number of optimization steps. The authors are going to address broader functionality and improved usability in the following stages of emDNA software development. This will offer users the choice of working within the framework of the 256 possible tetramer steps or the 16 possible dimer steps by including an expanded base-pair step option. Their initial analyses of the high-resolution structural data demonstrate that nucleotide context, or the immediate neighbors of a dimer step, affects the typical step-level characteristics and modifies the overall structure of sample DNA chains.

In conclusion, researchers and students now can access cutting-edge DNA modeling technology with the emDNA program developed by Professor Wilma Olson and her research team. General users will also be able to manipulate and view higher-order conformations of DNA using techniques that were previously only available to experts. These new technologies’ increased understanding of mesoscale organization may open up new research directions, such as ligand design that increases the possibility of stable loop formation and subsequent control of genetic processes.

emDNA – A Tool for Modeling Protein-decorated DNA Loops and Minicircles at the Base-pair Step Level - Medicine Innovates

About the author

Professor Wilma K. Olson, Ph.D. is the Mary I. Bunting Professor of Chemistry and Chemical Biology at Rutgers University. Her research focuses on the role that chemical architecture plays in determining the conformation, properties, and interactions of nucleic acids. She and her research team have found energetic and spatial codes embedded in the nucleotides within high-resolution DNA and RNA structures and have gained insight into the ease with which various parts of a double-helical molecule can fluctuate and how arbitrary nucleotide sequences respond to the proteins and small ligands that control the processing and packaging of genetic information. The Olson group has concomitantly developed a variety of theoretical and computational approaches that incorporate this local information in simulations of the structures and properties of long nucleic acid molecules. The work in the group has come to a point where one can generate ‘realistic’ representations of large assemblies of protein-decorated DNA molecules and relate the simulated configurations to assorted biophysical properties, such as the communication between chain ends and the interactions of sequentially distant DNA-bound proteins. The emDNA software is one of the advanced DNA modeling technologies developed by the Olson group and now available to users who wish to use the tool to gain a deeper understanding of DNA mesoscale organization and to pose new questions in genetic research.

About the author

Dr. Nicolas Clauvelin received his Ph.D. in Mechanical, Acoustic, and Electronic Sciences summa cum laude from the Université Pierre et Marie Curie (Paris VI), in 2008. Following postdoctoral work at Rutgers University, where he developed emDNA and other novel software to simulate the structures and properties of supercoiled DNA and chromatin, he joined Sendyne Corp., in 2015, and became its Chief Technical Officer in 2018. He is currently Director of Technology & SW Development at Sensata Technologies, which acquired Sendyne Corp. in 2021. Dr. Clauvelin’s expertise lies in modeling and simulating complex physical systems. He has studied a range of subjects in non-linear physics, biophysics, and electrochemistry, including complex mechanical structures (e.g., elastic beams with treatment of self-contact effects), biomolecular and biological assemblies (e.g., DNA and DNA-protein complexes), electrochemical and electrical systems (e.g., lithium-ion batteries, sensing devices). His work entails applied mathematics, software development and numerical methods, with a significant focus on differential equations, optimization, and control methods.

About the author

Dr. Robert T. Young received his Ph.D. in Chemistry and Chemical Biology from Rutgers University, in 2022, for thesis research on DNA deformability and the local features of DNA structure that influence genomic architecture and function. Dr. Young made extensive use of the emDNA software in studies of protein-mediated DNA looping, nucleosome-decorated DNA, and supercoiled DNA minicircles, as described in three recent papers. His mastery of the software combined with his expertise in teaching led to the development of the illustrative case studies and tutorials used in conjunction with the highlighted paper to introduce emDNA to new users.


Young RT, Clauvelin N, Olson WK. emDNA–A Tool for Modeling Protein-decorated DNA Loops and Minicircles at the Base-pair Step Level. Journal of Molecular Biology. 2022 Mar 24:167558.

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