Application Of in Silico Drug Design Approaches as A Channel to Uncover Strong Inhibitors of The MYL5 Protein Implicated in Cervical Cancer

Abstract

The Myosin regulatory light chain 5 (MYL5) protein plays a crucial role in the progression and metastasis of cervical cancer. MYL5, a phosphorylatable component of the myosin II ATPase motor complex, regulates cytoskeletal remodeling, cellular motility, proliferation, and transcriptional control through its calcium-binding EF-hand motifs. A positive feedback loop exists between MYL5 and hypoxia-inducible factor 1-alpha (HIF-1α), which upregulates MYL5 under hypoxic conditions, thereby promoting invasion, angiogenesis, and metastatic progression. Combining MYL5 inhibition with anti-angiogenic agents may overcome the limitations of monotherapy and reduce hypoxia-driven metastasis. The AlphaFold2 3D structure of the MYL5 protein is generated from the AlphaFold2 server and validated through ProSA and PROCHECK. Potential prognostic inhibitor ligands are selected after virtual screening and validated using SASA, MM-GBSA, and ADMET studies. Ligands L1 to L10 are proposed as potent inhibitors of the MYL5 protein by blocking the calcium-binding site, which prevents the cellular functions of MYL5 and thus inhibits hypoxia-induced cervical cancer metastasis.