Study on Doxorubicin interactions with Histone H1, using Molecular docking

The interaction of doxorubicin with histone H1, a key chromosomal protein, was investigated to shed light on the potential involvement of chromatin components in drug-chromatin interactions and their role in anthracycline-mediated tumor cell toxicity. Using atomic docking, we identified Asn19, Ser23, Ser24, Lys63, Ser68, and Ser70 as residues in close proximity to the doxorubicin ligand. Our findings suggest that van der Waals forces predominantly govern the histone H1-doxorubicin interaction, with no significant contribution from electrostatic forces. The calculated Gibbs free energy of this interaction (-6.3 kcal/mol) underscores the potential significance of histone H1-doxorubicin interactions in drug toxicity within tumor cells. The three-dimensional structure of the histone H1-doxorubicin interaction revealed multiple binding pockets for doxorubicin, highlighting histone H1 as a potential target for this anticancer drug. These insights into the mode of action of anthracyclines and the role of histones in tumor cell toxicity may pave the way for the development of novel therapeutic strategies targeting chromatin components. This study provides valuable information for understanding the molecular mechanisms underlying anthracycline activity and its implications for cancer therapy.