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. 2024 Sep 13;9(38):40061-40066.
doi: 10.1021/acsomega.4c05954. eCollection 2024 Sep 24.

CHIMERA_NA: A Customizable Mutagenesis Tool for Structural Manipulations in Nucleic Acids and Their Complexes

Affiliations

CHIMERA_NA: A Customizable Mutagenesis Tool for Structural Manipulations in Nucleic Acids and Their Complexes

Pradeep Pant. ACS Omega. .

Abstract

Studying the structure and dynamics of nucleic acids and their complexes is crucial for understanding fundamental biological processes and developing therapeutic interventions. However, the limited availability of experimentally characterized nucleic acid structures poses a challenge for exploring their properties comprehensively. To address this, we developed a customizable mutagenesis tool, CHIMERA_NA, to manipulate nucleic acid structures and their complexes. Utilizing the user-friendly CHIMERA_NA, researchers can perform mutations in nucleic acid structures, enabling the exploration of diverse structural configurations and dynamic behaviors. The tool offers the flexibility to generate all possible combinations of mutations or specific user-defined mutations based on research requirements. CHIMERA_NA leverages the capabilities of UCSF Chimera software, a widely used platform for molecular structure analysis, to facilitate the generation of mutations in nucleic acids. Our tool modifies the reference structure of nucleic acids or their complexes to generate initial coordinates of mutated structures/complexes within seconds for further computational exploration. This capability allows users to extend their investigations beyond structural repositories, enabling the study of DNA/RNA drug recognition, nucleic acid-protein interactions, and the intrinsic structural and dynamic properties of nucleic acids. By providing a user-friendly and customizable approach to nucleic acid mutagenesis, CHIMERA_NA contributes to advancing our understanding of nucleic acid biology and facilitating drug discovery efforts targeting nucleic acid-based mechanisms. CHIMERA_NA is freely available in the Supporting Information of this article.

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Conflict of interest statement

The author declares no competing financial interest.

Figures

Figure 1
Figure 1
CHIMERA_NA pipeline to generate mutant PDBs utilizing a reference PDB.
Figure 2
Figure 2
Input and output structures for Case 1 to Case 5 generated using the CHIMERA_NA approach. The site of interest is displayed in stick representation, while the rest of the molecule is shown in cartoon representation. Water molecules and ions of crystallization are removed for clarity.
Figure 3
Figure 3
Step-by-step procedure of executing CHIMERA_NA to generate the structures of mutants.

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