Research Article

Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights

Volume: 2026 Number: 2 July 28, 2026

Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights

Abstract

The Cluster of Differentiation 47 (CD47)–signal regulatory protein alpha (SIRPα) immune checkpoint is a key regulator of tumor immune evasion and a promising target in cancer immunotherapy. To overcome the limitations of monoclonal antibodies, this study aimed to identify high-affinity nucleic acid aptamers targeting CD47. A systematic single-nucleotide mutagenesis workflow was performed on a known CD47-binding DNA aptamer to generate 270 single-point variants, enabling unbiased evaluation of each nucleotide position. The variants were first screened for structural stability, yielding 81 structurally stable candidates. These candidates were then subjected to molecular docking against CD47, and 45 variants showed improved docking scores compared with the native aptamer. The docking score improved from −226.07 for the native aptamer to −301.94 for the best-performing variant. Based on structural stability and docking performance, the ten top-ranked candidates were selected for molecular dynamics simulations. These variants exhibited improved conformational stability, as reflected by lower root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) values and increased hydrogen bonding, with Seq198 and Seq262 showing the most stable profiles. Binding free energy calculations confirmed improved affinity. The native aptamer exhibited a ΔTOTAL of −97.16 kcal/mol, whereas Seq198 (−173.13 kcal/mol), Seq244 (−152.35 kcal/mol), and Seq112 (−147.19 kcal/mol) showed markedly stronger binding. Seq198 emerged as the most promising candidate. These findings demonstrate that systematic computational mutagenesis is an effective strategy for optimizing aptamer performance and identifying high-affinity CD47-targeting candidates.

Keywords

Thanks

The authors gratefully acknowledge the use of the High Performance and Grid Computing Center (TRUBA resources) provided by the Scientific and Technological Research Council of Türkiye (TÜBİTAK) during this study.

References

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Details

Primary Language

English

Subjects

Theoretical and Computational Chemistry (Other), Biomolecular Modelling and Design

Journal Section

Research Article

Publication Date

July 28, 2026

Submission Date

February 18, 2026

Acceptance Date

June 3, 2026

Published in Issue

Year 2026 Volume: 2026 Number: 2

APA
Altunok, S., Buluz, E. C., & Aymaz, E. M. (2026). Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. Journal of the Turkish Chemical Society Section A: Chemistry, 2026(2), 1-17. https://doi.org/10.18596/jotcsa.1892713
AMA
1.Altunok S, Buluz EC, Aymaz EM. Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. JOTCSA. 2026;2026(2):1-17. doi:10.18596/jotcsa.1892713
Chicago
Altunok, Sümeyye, Emre Can Buluz, and Ehed Muhammed Aymaz. 2026. “Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights”. Journal of the Turkish Chemical Society Section A: Chemistry 2026 (2): 1-17. https://doi.org/10.18596/jotcsa.1892713.
EndNote
Altunok S, Buluz EC, Aymaz EM (July 1, 2026) Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. Journal of the Turkish Chemical Society Section A: Chemistry 2026 2 1–17.
IEEE
[1]S. Altunok, E. C. Buluz, and E. M. Aymaz, “Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights”, JOTCSA, vol. 2026, no. 2, pp. 1–17, July 2026, doi: 10.18596/jotcsa.1892713.
ISNAD
Altunok, Sümeyye - Buluz, Emre Can - Aymaz, Ehed Muhammed. “Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights”. Journal of the Turkish Chemical Society Section A: Chemistry 2026/2 (July 1, 2026): 1-17. https://doi.org/10.18596/jotcsa.1892713.
JAMA
1.Altunok S, Buluz EC, Aymaz EM. Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. JOTCSA. 2026;2026:1–17.
MLA
Altunok, Sümeyye, et al. “Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights”. Journal of the Turkish Chemical Society Section A: Chemistry, vol. 2026, no. 2, July 2026, pp. 1-17, doi:10.18596/jotcsa.1892713.
Vancouver
1.Sümeyye Altunok, Emre Can Buluz, Ehed Muhammed Aymaz. Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. JOTCSA. 2026 Jul. 1;2026(2):1-17. doi:10.18596/jotcsa.1892713