Discovery of Potential GPRC5D Inhibitors through Virtual Screening and Molecular Dynamics Simulations.
Uncover potential GPRC5D inhibitors - a promising target for blood cancer treatment. Rigorous virtual screening and simulations identify 4 top candidates, with compound 2 showing strong binding and drug-likeness. This breakthrough could pave the way for novel immunotherapies.
This study developed a multistep computational screening strategy to identify small-molecule inhibitors targeting GPRC5D, a promising target for immunotherapy in hematologic malignancies. The workflow integrated various computational tools, including PLANET, Vina-GPU, MM/GBSA, and admetSAR 3.0, along with molecular dynamics simulations and absolute binding free energy calculations. From an initial library of 8,617 compounds, four top candidates were prioritized, with compound 2 exhibiting strong binding affinity and high drug-likeness. The findings provide a systematic approach to accelerate the discovery of GPRC5D-targeted therapeutics, potentially leading to new treatment options for blood cancers like multiple myeloma.