Molecular docking of human serum albumin with penicillin G determinants

  • N. V. Khmil Usikov Institute for Radiophysics and Electronics, NAS of Ukraine, 12 Acad. Proskura Str., Kharkiv, 61085, Ukraine; Kharkiv National University of Radio Electronics, 14 Nauky Ave., Kharkiv, 61166, Ukraine
  • V. G. Kolesnikov Usikov Institute for Radiophysics and Electronics, NAS of Ukraine, 12 Acad. Proskura Str., Kharkiv, 61085, Ukraine
Keywords: human serum albumin, penicillin G determinants, immediate hypersensitivity reactions, molecular docking


Background: Human serum albumin (HSA) is the main pharmacokinetic effector of many medications, including penicillin G and its metabolites. An urgent problem of practical medicine is immediate hypersensitivity reactions caused by penicillin toxicity (about 8 % compared to other medications), accompanied by skin pathology, anaphylaxis, and fatality.

Objectives: The aim of this study is to describe the structures of penicillin G determinants-HSA complexes and to identify favorable binding sites and the amino acid residues involved in the interaction. 

Material and Methods: The crystal structure of HSA (ID: 1AO6 from Protein Data Bank) ( was chosen as a docking target. Molecular docking methods (AutoDock Tools 1.5.7, AutoDock Vina 1.1.2) were used to gain insight into the interaction of HSA with the major (benzyl penicilloyl G, penicillanic acid) and minor (penicillamine, penicilloic acid, penilloic acid) determinants of penicillin G. Visualization of docking results was implemented in PyMol 2.5. The Protein Plus server ( was used to evaluate potential binding pockets. The PLIP tool ( was used to identify non-covalent interactions between HSA and its ligands. 

Results: The molecular docking data indicate that the major determinants of penicillin G are involved in the formation of hydrogen bonds with such HSA residues as Trp214, Arg218, His242, and Asn295; for the minor determinants — Asp108, His146, Tyr148, Ser193, Arg197, Gln204. Both types of determinants are located in the hydrophobic cavity of subdomains IIA and IB. Hydrophobic interactions are present mainly between penicillin G determinants and amino acid residues of subdomain IIIA, such as Ala350, Asp451, Tyr452, and Gln459.

Conclusion: The study of penicillin G determinants-HSA complexes is important in the pathogenesis of antibiotic allergy. Identification of specific binding sites can be useful for the development and synthesis of new immunogenic antigens (complexes of major and minor determinants of penicillin G with HSA) that can stimulate the immune system and produce specific antibodies to prevent allergic reactions.


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How to Cite
Khmil, N. V., & Kolesnikov, V. G. (2023). Molecular docking of human serum albumin with penicillin G determinants. Biophysical Bulletin, (49), 7-19.
Molecular biophysics