Computational evaluation of the interactions of natural compounds with the RNA binding domain of nucleolins using molecular docking and molecular dynamics simulations

Nucleolin has been proposed as an alternative target to search for and design possible new antitumor or anticancer therapies. Our objective was to evaluate compounds with potential binding affinities to the RNA binding domain (RBD) of nucleolins using bioinformatics tools. Ten compounds were evaluated of which three molecules (betulinic acid, triptolide, and berberine) showed binding affinities to the RBD domain with significantly favorable (p<0.05) binding energy values and calculated dissociation constant (K-d (calc)) between 0.14-0.91 mu M. Molecular dynamics simulations evidenced that only the nucleolin-berberine complex exhibited interaction stability and favorable binding free energy in the simulated time. The residues involved in the complex formation were amino acids that play important roles in the active site. These findings suggest that among the evaluated compounds, berberine showed favorable results as a potential inhibitor of nucleolin activities, specifically in the RBD domain.