Skip to main content
Journal cover image

Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions.

Publication ,  Journal Article
Umuhire Juru, A; Patwardhan, NN; Hargrove, AE
Published in: ACS chemical biology
May 2019

The implication of RNA in multiple cellular processes beyond protein coding has revitalized interest in the development of small molecules for therapeutically targeting RNA and for further probing its cellular biology. However, the process of rationally designing such small molecule probes is hampered by the paucity of information about fundamental molecular recognition principles of RNA. In this Review, we summarize two important and often underappreciated aspects of RNA-small molecule recognition: RNA conformational dynamics and the biophysical properties of interactions of small molecules with RNA, specifically thermodynamics and kinetics. While conformational flexibility is often said to impede RNA ligand development, the ability of small molecules to influence the RNA conformational landscape can have a significant effect on the cellular functions of RNA. An analysis of the conformational landscape of RNA and the interactions of individual conformations with ligands can thus guide the development of new small molecule probes, which needs to be investigated further. Additionally, while it is common practice to quantify the binding affinities ( Ka or Kd) of small molecules for biomacromolecules as a measure of their activity, further biophysical characterization of their interaction can provide a deeper understanding. Studies that focus on the thermodynamic and kinetic parameters for interaction between RNA and ligands are next discussed. Finally, this Review provides the reader with a perspective on how such in-depth analysis of biophysical characteristics of the interaction of RNA and small molecules can impact our understanding of these interactions and how they will benefit the future design of small molecule probes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

ACS chemical biology

DOI

EISSN

1554-8937

ISSN

1554-8929

Publication Date

May 2019

Volume

14

Issue

5

Start / End Page

824 / 838

Related Subject Headings

  • Thermodynamics
  • Small Molecule Libraries
  • RNA
  • Organic Chemistry
  • Nucleic Acid Conformation
  • Molecular Conformation
  • Ligands
  • Kinetics
  • 34 Chemical sciences
  • 31 Biological sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Umuhire Juru, A., Patwardhan, N. N., & Hargrove, A. E. (2019). Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions. ACS Chemical Biology, 14(5), 824–838. https://doi.org/10.1021/acschembio.8b00945
Umuhire Juru, Aline, Neeraj N. Patwardhan, and Amanda E. Hargrove. “Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions.ACS Chemical Biology 14, no. 5 (May 2019): 824–38. https://doi.org/10.1021/acschembio.8b00945.
Umuhire Juru A, Patwardhan NN, Hargrove AE. Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions. ACS chemical biology. 2019 May;14(5):824–38.
Umuhire Juru, Aline, et al. “Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions.ACS Chemical Biology, vol. 14, no. 5, May 2019, pp. 824–38. Epmc, doi:10.1021/acschembio.8b00945.
Umuhire Juru A, Patwardhan NN, Hargrove AE. Understanding the Contributions of Conformational Changes, Thermodynamics, and Kinetics of RNA-Small Molecule Interactions. ACS chemical biology. 2019 May;14(5):824–838.
Journal cover image

Published In

ACS chemical biology

DOI

EISSN

1554-8937

ISSN

1554-8929

Publication Date

May 2019

Volume

14

Issue

5

Start / End Page

824 / 838

Related Subject Headings

  • Thermodynamics
  • Small Molecule Libraries
  • RNA
  • Organic Chemistry
  • Nucleic Acid Conformation
  • Molecular Conformation
  • Ligands
  • Kinetics
  • 34 Chemical sciences
  • 31 Biological sciences