Nav: Home

New dynamic probes for ions interacting with biomolecules

January 10, 2019

Pairs of negatively charged phosphate groups and positive magnesium ions represent a key structural feature of DNA and RNA embedded in water. Vibrations of phosphate groups have now been established as selective probes of such contact pairs and allow for a mapping of interactions and structure on the ultrafast time scales of molecular dynamics.

DNA and RNA are charged polymers that encode genetic information in a double helix structure and act as key player in the biosynthesis of proteins. Their negative charges are located in the molecular backbone, which consists of ionic phosphate (PO2-) and of sugar groups (Figure 1). Stabilization of the macromolecular structures of DNA and RNA requires a compensation of strong repulsive electric forces between the equally charged phosphate groups by ions of opposite, i.e., positive charge. In this context, magnesium (Mg2+) ions are particularly relevant as they not only stabilize the structure but also mediate the recognition of external binding partners and act as catalytic centers. Moreover, changes of macromolecular structure via dynamic folding processes are connected with a rearrangement of positive ions embedded in the surrounding water shell.

Positive ions are arranged in different geometries around DNA and RNA: in so-called site-bound or contact-pair geometries, a positive ion is located in direct contact with an oxygen atom of a phosphate group. In contrast, the so-called outer ion atmosphere consists of positive ions separated by at least one layer of water molecules from the phosphate groups. The functional role of the different geometries and the underlying interactions are far from being understood. A deeper insight at the molecular level requires highly sensitive probes which allow for discerning the different ion geometries without disturbing them, and for mapping their dynamics on the ultrafast time scale of molecular motions.

In a recent publication, researchers from the Max Born Institute (MBI) demonstrate that vibrations of phosphate groups represent sensitive and noninvasive probes of ion geometries in a water environment. Dimethylphosphate (DMP, (CH3O)2PO2-), an established model system for the DNA and RNA backbone, was prepared in liquid water with an excess of Mg2+ ions (Figure 2, top) and studied by nonlinear vibrational spectroscopy in the femtosecond time domain (1 fs = 10 to the power of -15 s). The experiments make use of two-dimensional infrared (2D-IR) spectroscopy, a most sophisticated method for analyzing the ionic interactions and structures on the intrinsic time scale of fluctuating molecular motions.

The experiments map Mg2+ ions in direct contact with a PO2- group via a distinct feature in the 2D-IR spectrum (Figure 2, bottom). The interaction with the Mg2+ ion shifts the asymmetric PO2- stretching vibration to a frequency which is higher than in absence of Mg2+ ions. The lineshape and the time evolution of this new feature reveal fluctuations of the contact ion pair geometry and the embedding water shell on a time scale of hundreds of femtoseconds while the contact pair itself exists for much longer times (~10 to the power of -6 s). An in-depth theoretical analysis shows that the subtle balance of attractive electrostatic (Coulomb) forces and repulsive forces due to the quantum-mechanical exchange interaction govern the frequency position of the phosphate vibration.

The ability of 2D-IR spectroscopy to characterize the short-ranged phosphate-ion interaction in solution provides a novel analytical tool that complements currently available structural techniques. An extension of this new approach to DNA and RNA and their ionic environment is most promising and expected to provide new insight in the forces stabilizing equilibrium structures and driving folding processes.

Forschungsverbund Berlin

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...