Fascinating Structure of Holliday Junction: The Crux of DNA Biophysics Studied by Molecular Dynamics Simulations
Project Number: 25-16134S
Principal Investigator: RNDr. Miroslav Krepl, Ph.D.
Funding Agency: Czech Science Foundation (GA ČR)
Project Duration: 2025–2027
Institution: Institute of Biophysics of the Czech Academy of Sciences, v.v.i.
Project Description
The project focuses on a detailed investigation of the so-called Holliday Junction (HJ), a unique four-stranded DNA structure that plays a crucial role in DNA repair and in the exchange of genetic information between chromosomes. These processes are essential for genome stability, cell survival, and the genetic variability of organisms. Although the biological importance of these structures is well established, their dynamic behavior and structural properties remain only partially understood.
The main objective of the project is to employ advanced computational approaches, particularly molecular dynamics simulations, to provide a detailed atomistic description of the structure, motions, and interactions of the Holliday Junction. The research will address several key aspects, including transitions between different conformational states, the process known as branch migration (movement of the DNA strand exchange point), and interactions with proteins that regulate these processes in the cell.
An important component of the project is the application of the acquired knowledge in the field of DNA nanotechnology. Holliday Junctions serve as fundamental building blocks for constructing nanoscale structures and materials. A deeper understanding of their properties may enable more efficient design of novel functional nanostructures with potential applications in medicine and nanoelectronics.
The project builds on the team’s previous successful research and introduces innovations both in simulation methodologies and in the interpretation of experimental data. Expected outcomes include a significant advancement in understanding DNA dynamics, publications in high-impact scientific journals, and strengthened international collaborations.
Overall, the project will contribute to a better understanding of fundamental biological processes and support the development of modern DNA-based technological applications.
Prebiotic route to informational polymers based on H-phosphonate chemistry
Project Number: 1319776
Principal Investigator: Judit E. Šponer (PI) in collaboration with Matthew Pasek (co-PI) (Rensselaer Polytechnic Institute, Troy, USA)
Funding Agency: Human Frontier Science Program
Project Duration: 1. 7. 2025 – 31. 6. 2028
Institution: Institute of Biophysics of the Czech Academy of Sciences, v.v.i.
Project Description
In the frame of this project we address one of the central problems surrounding life's origin on our planet, i.e., how the first genetic polymers, likely nucleic acids, were synthesized from simple prebiotic building blocks. Previous approaches dealing with this subject tried to reconstruct the road to the first oligonucleotide sequences using nucleotide monomers that contain phosphorus in the +5 oxidation state.
Recent investigations on prebiotic phosphorus chemistry suggest that phosphorus compounds of lower oxidation state could be more relevant in a reducing primordial geochemical environment. Since these compounds are chemically more active than those in the highest (+5) oxidation form, it seems reasonable to assume that reduced-form nucleotide monomers, like nucleoside H-phosphonates, may exhibit higher propensity to oligomerize.
Motivated by this we investigate the processes that could lead to the formation, accumulation and polymerization of these compounds in a realistic geological context that likely existed on the early Earth. Our ultimate goal is to reconstruct a prebiotic scenario that outlines a geochemically plausible route leading from simple precursors like nucleosides up to functional RNA-like oligomers through the chemistry of reduced phosphate compounds, especially those having phosphorus in the +3 oxidation state.
Crystallization non-equilibria to accumulate and polymerize RNA in early evolution
Project Number: 25-16127K
Principal Investigator: Judit E. Šponer (PI) in collaboration with Dieter Braun (co-PI) (Ludwig-Maximilians-Universität München)
Funding Agency: Czech Science Foundation (GA ČR) in collaboration with Deutsche Forschungsgemeinschaft
Project Duration: 1. 4. 2025 – 31. 3. 2028
Institution: Institute of Biophysics of the Czech Academy of Sciences, v.v.i.
Project Description
Understanding how simple organic precursor molecules were selected and accumulated from a supposedly highly complex prebiotic pool is one of the central problems of the research addressing life's origins.
Previous investigations suggested that nucleotides of low solubility could be sequestered from the prebiotic pool through crystallization or accumulation in thermal traps, like rock pores. In the frame of this project we combine these two approaches to study how the synergic effect of organic crystallization and non-equilibrium physical phenomena likely existing in a primordial environment could aid the selective accumulation of the first nucleic acid and peptide molecules and their precursors.
Thus, the ultimate aim is to reconstruct a prebiotic scenario, how organic crystallization in a non-equilibrium system represented by rock pores exposed to thermal gradients could lead to the spatial separation and accumulation of nucleotides, amino acids and their oligomers that made the foundations of terrestrial life.