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Abstract Topoisomerase enzymes are vital players in DNA manipulation, crucial for maintaining its topological structure, and a cornerstone of molecular biology. Among these enzymes, Topoisomerase-IB (Topo-IB) has a unique role in relieving DNA torsional stress using phosphorylated tyrosine bonds (PTR), which are crucial for changing DNA topology. Our study, employing molecular dynamics simulations and diverse analytical tools, delves into the structural intricacies governing Topo-IB activity. Key to our findings is the discovery of Lysine 318 (Lys 318) within the core domain as a major contributor to Topo-IB's function. Lys 318's role in generating polar solvation energy crucially stabilizes enzymatic activity. Furthermore, we highlight the pivotal role of hydrogen bond dynamics in orchestrating Topo-IB's activity, showcasing the intricate interplay of molecular interactions during DNA manipulation. Overall, our study unveils the molecular mechanisms driving Topo-IB's function, spotlighting Lys 318 and hydrogen bond dynamics as central elements. These insights deepen our grasp of DNA topology modulation and offer promising avenues for developing pharmacological interventions targeting Topo-IB, with implications across various pathophysiological contexts.
dhar et al. (Fri,) studied this question.