Conversely, residues such as Met83, Thr94, Gly120, Val121, and Phe123 displayed significant fluctuations in contact frequency between the two intervals, highlighting dynamic alterations in their binding patterns (Figure ). Changes in receptor-ligand interactions are observed during the later simulation phase (6.5 -8.5 µs), where a larger number of residues interacted with the ligand as compared to the initial 6 µs of simulation (Figure , 11b, and Supplementary Table ). Such a shift in the interaction land-scape with a different ensemble of residues suggests a potential ligand rearrangement within the binding pocket, and a dynamicity of ligand 1 in the binding pocket of the receptor-ligand complex may contribute to an extended residence time of ligand 1. To interpret the binding strength and specificities of the two Hsp90ligand complexes, residues interacting with the ligand within a cutoff distance of 4 Å were monitored at 0.4 ns intervals for the entire duration of the simulation. It is observed that ligand 1 interacted with a significantly higher number of residues than ligand 9 (Figure , 11b, 11c and Supplementary Table ). Interactions, such as hydrogen bonds, hydrophobic interactions, and van der Waals forces, potentially account for a higher residence time of ligand 1. On the contrary, reduced ligand-residue interactions for ligand 9 correlate well with its lower residence time, suggesting fewer constraints holding it in the binding pocket.