Combined All-Atom Simulations and Biophysical Assays Uncover Loop-Driven Stabilization in the HRAS i-motif
Alhadji Malloum1,2, Valentina Arciuolo3, Pavlína Pokorná4
1Department of Chemistry, University of the Free State, Bloemfontein 9301, South Africa.
Journal of Chemical Information and Modeling
|March 4, 2026
Summary
DNA i-motifs are flexible structures. This study reveals the intricate conformational dynamics of the HRAS gene promoter i-motif (iHRAS), highlighting its multiple states and loop flexibility influenced by potassium ions.
Area of Science:
- Molecular Biology
- Biophysics
- Genomics
Background:
- I-motifs are noncanonical DNA secondary structures.
- Stabilized by hemiprotonated C+:C base pairs.
- Flexibility and heterogeneity challenge structural characterization.
Purpose of the Study:
- Characterize the structure and dynamics of the i-motif monomer from the HRAS gene promoter (iHRAS).
- Investigate the conformational behavior of iHRAS using computational and experimental methods.
Main Methods:
- All-atom molecular dynamics simulations.
- Biophysical experimental techniques.
- Structural and dynamic analysis of iHRAS.
Main Results:
- iHRAS exhibits complex conformational dynamics with multiple interconverting states.
- The i-motif core is stabilized by a G:G cap, with variable C+:C base pair content.
- Loop regions display significant heterogeneity, sampling base-exposed states facilitated by K+ ion binding.
Conclusions:
- The study provides a detailed understanding of iHRAS structure and dynamics.
- Findings elucidate the role of environmental factors like K+ ions in i-motif conformation.
- Contributes to understanding the biological relevance of i-motif structures in gene regulation.
Related Concept Videos
01:58Cooperative Allosteric Transitions
3.2K
3.2K
01:58Cooperative Allosteric Transitions
9.2K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
9.2K
01:58Cooperative Allosteric Transitions
2.8K
2.8K
01:07Damped Oscillations
7.4K
In the real world, oscillations seldom follow true simple harmonic motion. A system that continues its motion indefinitely without losing its amplitude is termed undamped. However, friction of some sort usually dampens the motion, so it fades away or needs more force to continue. For example, a guitar string stops oscillating a few seconds after being plucked. Similarly, one must continually push a swing to keep a child swinging on a playground.
Although friction and other non-conservative...
Although friction and other non-conservative...
7.4K
01:06Forced Oscillations
8.1K
When an oscillator is forced with a periodic driving force, the motion may seem chaotic. The motions of such oscillators are known as transients. After the transients die out, the oscillator reaches a steady state, where the motion is periodic, and the displacement is determined.
8.1K
01:24Pole and System Stability
1.1K
The transfer function is a fundamental concept representing the ratio of two polynomials. The numerator and denominator encapsulate the system's dynamics. The zeros and poles of this transfer function are critical in determining the system's behavior and stability.
Simple poles are unique roots of the denominator polynomial. Each simple pole corresponds to a distinct solution to the system's characteristic equation, typically resulting in exponential decay terms in the system's...
Simple poles are unique roots of the denominator polynomial. Each simple pole corresponds to a distinct solution to the system's characteristic equation, typically resulting in exponential decay terms in the system's...
1.1K