Investigation of the Interactions of Methyl-β-Cyclodextrin and Amphotericin B with Erythrocyte Membrane Components by Molecular Docking

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Abstract

The aim of this work was to analyze the interactions of methyl-β-cyclodextrin and amphotericin B (AmB) with spectrin, actin, and hemoglobin by the method of molecular docking. The protein structures were taken from PDB. The full-atom models of proteins were "cleaned" from water molecules and buffer components, surface charge arrangement was performed, and cells were selected for "blind" docking. The structural formula of methyl-β-cyclodextrin and amphotericin B were taken from PubChem and converted to HyperChem. Geometry optimization was performed using the MM+ model potential, rigid/fixed structures were optimized using the semi-empirical quantum chemical method PM3. The protein-ligand complex interactions were described using PLIP. The total binding energy for all complexes ranged from –4.4 to –10.3 kcal/mol. The complexes were formed due to hydrogen, van der Waals bonds, and salt bridges. Visualization of the most energetically advantageous positions confirmed that both amphotericin B and methyl-β-cyclodextrin localized in the central cavities of hemoglobin and actin, and in the distal sites of α- and β-subunits of spectrin. Amphotericin B formed more stable complexes with each of the proteins: the strength of hydrogen bonds and the number of hydrophobic contacts with the proteins were higher than for complexes with methyl-β-cyclodextrin.

About the authors

L. O Sokolova

Voronezh State University

Email: lyudmila.sokolova.94@mail.ru
Voronezh, Russia

M. S Kondratyev

Voronezh State University; Institute of Cell Biophysics, Russian Academy of Sciences

Voronezh, Russia; Pushchino, Russia

E. A Kalaeva

Voronezh State University

Voronezh, Russia

V. G Artyukhov

Voronezh State University

Voronezh, Russia

M. A Nakvasina

Voronezh State University

Voronezh, Russia

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