Computer screening of peptidomimetics and small-molecule ligands of B-cell membrane proteins for therapy of Burkitt lymphoma
DOI:
https://doi.org/10.61751/bmbr/4.2023.25Keywords:
molecular docking, pharmacophores, antibodies, mimetics, immunogenicityAbstract
The capabilities of molecular modelling and docking allow for the discovery of new potential drug agents
to improve the treatment of diseases, which is a current concern. The objective of this study was to conduct in silico
screening for antibody mimetics to B-cell membrane proteins for the treatment of Burkitt lymphoma through virtual
screening. In this work, a standard protocol for structure-based virtual screening was employed, with the distinction that
pharmacophores for screening were built not based on small-molecule ligands but on selected amino acid residues of
antibodies. Based on literature data and the presence of a mechanism of direct cytotoxic action, as well as the availability of
3D structures of complexes, three monoclonal antibodies were selected: obinutuzumab, epratuzumab, and atezolizumab.
The identification of biological targets was carried out by searching for 3D structures of selected complexes with target
proteins in the Protein Data Bank. For virtual screening, the web service Pharmit was chosen. Using the Molecular
Operating Environment program, pharmacophore models were constructed for three complexes: CD20 and obinutuzumab,
CD22 and epratuzumab, and PD-L1 and atezolizumab. Docking with the CD20, CD22, and PD-L1 proteins was conducted
at the binding sites recognised by the original antibody. Through in silico virtual screening using the Molecular Operating
Environment software, a search for antibody mimetics to B-cell membrane proteins for Burkitt lymphoma treatment
was conducted, resulting in the selection of 5 potential anti-lymphoma agents: CHEMBL505179 for the CD20 receptor,
an antagonist of the melanocortin receptor for CD20 (PubChem-44406884), an inhibitor of blood clotting Factor Xa for
CD22 (PubChem-136510605), and a blocker of epithelial Na+ channels for CD22 (PubChem-126761430), and an agonist
of the melanocortin receptor for PD-L1 (PubChem-25078192). The obtained results can be applied in the pharmaceutical
industry and oncological practice to enhance therapeutic outcomes in the treatment of patients with Burkitt lymphoma
Received: 31.07.2023 | Revised: 11.10.2023 | Accepted: 28.11.2023
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