In silico analysis of resveratrol induced PD-L1 dimerisation

Authors

  • Viktor A. Urban Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus
  • Alexander I. Davidovskii Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus
  • Valery G. Veresov Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus https://orcid.org/0000-0001-5884-4722

Keywords:

PD-1, PD-L1, resveratrol, computational structural biology
Supporting Agencies
This work was supported by the Belarusian state program for biotechnology (grant No. 1.45).

Abstract

T-cell activation through the blockade of PD-1 – PD-L1 interactions is recognised at present as one of the most promising strategies in the cancer treatment and a number of antibodies targeting the PD-1 – PD-L1 immune checkpoint pathway have been approved after successful clinical trials. However, the use of antibodies suffers from a number of shortcomings including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs. Small molecule based therapeutic approaches offer the potential to address the shortcomings of the antibody-based checkpoint inhibitors. At present, more than twenty small molecular inhibitors of the PD-1 – PD-L1 interactions whose scaffold is based on substituted biphenyl group connected to a further aromatic ring through a benzyl ether bond have been identified and patented by Bristol – Mayers – Squibb (USA). Structural studies have shown that all these compounds act by inducing the dimerisation of PD-L1 that makes PD-L1 non-competent for forming complex with PD-1. Very recently, the dietary polyphenol resveratrol (RSV) has been reported to inhibit the PD-1 – PD-L1 interactions through the induction of the PD-L1 dimerisation but the mechanisms remain unclear. Here, computational structural biology tools combining protein – protein and protein – ligand docking with molecular dynamics simulations were used to gain structural insights into the mechanisms of the RSV-induced dimerisation of PD-L1.

Author Biographies

  • Viktor A. Urban, Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus

    junior researcher at the laboratory of immunology and cell biophysics

  • Alexander I. Davidovskii, Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus

    junior researcher at the laboratory of immunology and cell biophysics

  • Valery G. Veresov, Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, 27 Akademičnaja Street, Minsk 220072, Belarus

    doctor of science (biology); chief researcher at the laboratory of immunology and cell biophysics

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Published

2021-03-12

Issue

No. 1 (2021): Journal of the Belarusian State University. Biology

Section

Biochemistry

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How to Cite

Urban, V. A. ., Davidovskii, A. I. ., & Veresov, V. G. . (2021). In silico analysis of resveratrol induced PD-L1 dimerisation. Experimental Biology and Biotechnology, 1, 39-47. https://doi.org/10.33581/2521-1722-2021-1-39-47