New Insight Into The Structural Changes Of Apoferritin Pores In The Process Of Doxorubicin Loading At An Acidic PH: Molecular Dynamics Simulations

Abstract

Apoferritin (APO-Fr) is one of the most investigated proteins proposed as an advanced structure for drug delivery systems. Herein, molecular dynamics simulation was employed to compare the opening of 3-fold and 4-fold pores in APO-Fr during the partial disassembly process at an acidic pH. We showed that more hydrophilic residues in the surface of 3-fold pores compared to 4-fold pores facilitate increased flexibility and a higher tendency to open. In particular, dissociation is induced by the presence of Doxorubicin (DOX) close to 3-fold pores. Our simulations showed loaded DOXs on the APO-Fr surface were mainly involved in the hydrogen bond interactions with the hydrophilic residues, suggesting the difficulty of hydrophobic drugs loading in APO-Fr with the partial disassembly process. However, π-π interactions as well as hydrogen bonds between protein and DOXs were mediated by the basic and acidic amino acids such as HIP128, GLU17, and LYS143 at the open pores, providing penetration of DOXs into the H-Apo-Fr. We conclude that increased drug encapsulations and loading capacity of hydrophobic drugs into the cavity of APO-Fr are feasible by further disassembly of openings to access the internal hydrophobic portions of the protein.

Department(s)

Chemical and Biochemical Engineering

Comments

Mazandaran University of Medical Sciences, Grant 9216

Keywords and Phrases

Apoferritin; Disassembly process; Doxorubicin; Drug delivery; Drug loading; Molecular dynamics simulation

International Standard Serial Number (ISSN)

1879-0534; 0010-4825

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 Elsevier, All rights reserved.

Publication Date

01 Feb 2022

PubMed ID

34952337

Link to Full Text

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