Molecular Dynamics Investigation of Bcl-xL Interactions with Potential Cancer Inhibiting Compounds
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The Bcl-xL protein belongs to the Bcl-2 family of proteins. Bcl-xL is reportedly actively involved in cancer, along with various other factors. Since it has been revealed that this protein plays an active role in cancer, it can be a potential drug target to inhibit cancer activity. Its overexpression can lead to the evasion of apoptosis, allowing cancer cells to persist and proliferate uncontrollably. Hence, targeting Bcl-xL is a promising strategy in cancer therapy, while aiming to induce apoptosis in cancer cells and inhibiting their survival mechanism. In the current study, reported Bcl-xL inhibitors were evaluated for their stability, binding specificity, and interaction dynamics by performing molecular dynamics (MD) simulations. The compounds 24 and 54 revealed stable hydrogen bonding and hydrophobic interactions with active residues in the hydrophobic binding pocket. The binding sites were elucidated for the Bcl-xL protein. Exploring the molecular structural properties involved in binding provides mechanistic insights. This understanding aids in unraveling the protein-ligand interactions crucial for inhibiting anti-apoptotic proteins like Bcl-xL, offering potential for developing targeted inhibitors with anticancer properties.
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