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Related Experiment Video

Updated: Sep 13, 2025

Analyzing and Building Nucleic Acid Structures with 3DNA
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A Generalized Framework for Developing Dihedral Torsion Energy Terms in Nucleic Acids Force Fields.

Chungwen Liang1, David Pekker1,2, Alessio Valentini1

  • 1Creyon Bio Inc., Carlsbad, California 92010, United States.

Journal of Chemical Theory and Computation
|July 31, 2025
PubMed
Summary

Researchers developed Creyon25, a versatile force field (FF) model for biomolecular simulations. This new FF accurately models natural and modified nucleic acids, advancing oligonucleotide therapy development.

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Area of Science:

  • Biomolecular modeling
  • Computational chemistry
  • Structural biology

Background:

  • Accurate force fields (FFs) are crucial for simulating large biomolecular systems.
  • Existing nucleic acid FFs lack a universal framework for natural and modified variants across diverse environments.
  • Developing robust FFs is essential for advancing oligonucleotide-based therapies.

Purpose of the Study:

  • To introduce a general methodology for developing torsional energy parameters applicable to all nucleic acid systems.
  • To create a force field (FF) generalizable to chemically modified nucleic acids.
  • To achieve accurate conformational simulations of nucleic acids in physiological conditions.

Main Methods:

  • Developed a general methodology for parametrizing key dihedral angles in nucleic acids.
  • Simultaneously parametrized torsional energy parameters for nucleic acid systems.
  • Validated the resulting force field, Creyon25, across various RNA and DNA structures.

Main Results:

  • The Creyon25 force field demonstrates accuracy comparable to established AMBER and CHARMM models.
  • The developed framework is generalizable to chemical modifications in nucleic acid linkers, sugars, and bases.
  • The Creyon25 RNA model accurately reproduces experimentally observed structures; the DNA model shows potential for improvement.

Conclusions:

  • This work represents a significant advancement in creating robust force fields for chemically modified nucleic acids.
  • The Creyon25 FF supports the development and application of oligonucleotide therapies.
  • The generalized methodology paves the way for future FF development for diverse nucleic acid systems.