Is the Triggering of PD-L1 Dimerization a Potential Mechanism for Food-Derived Small Molecules in Cancer Immunotherapy? A Study by Molecular Dynamics.

ABSTRACT: Using small molecules to inhibit the PD-1/PD-L1 pathway is an important approach in cancer immunotherapy. Natural compounds such as capsaicin, zucapsaicin, 6-gingerol and curcumin have been proposed to have anticancer immunologic functions by downregulating the PD-L1 expression. PD-L1 dimerization promoted by small molecules was recently reported to be a potential mechanism to inhibit the PD-1/PD-L1 pathway. To clarify the molecular mechanism of such compounds on PD-L1 dimerization, molecular docking and molecular dynamics simulations were performed. The results evidenced that these compounds could inhibit PD-1/PD-L1 interactions by directly targeting PD-L1 dimerization. Binding free energy calculations showed that capsaicin, zucapsaicin, 6-gingerol and curcumin have strong binding ability

SUBMITTER: Wu X 

PROVIDER: S-EPMC9864258 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature