Rotatable bonds
The docking simulation samples different positions of the ligand in the binding site as well as different combinations of rotations around single bonds in the ligand. The more rotatable/flexible bonds a ligand have, the more different combinations to test. If a ligand has more than around eight rotatable (flexible) bonds, it can require much more sample iterations to find the optimal binding mode.
The number of rotatable (flexible) bonds can be seen in the Property viewer when selecting a Docking result in the Project Tree, or from the Flexible bonds column in Docking results tables.
If the ligand has many flexible bonds, make sure that all single bonds in the molecule can actually be expected to have low energy barriers for rotation, otherwise, change the single bond into a delocalized bond as for delocalized pi-systems (using options from the right-click context menu on one of the atoms participating in the bond). In this way the initial geometry for this part of the molecule will be kept during the docking simulation.
To increase the chance of observing the correct binding mode for a ligand with many rotatable bonds, you can try increasing the number of docking simulation iterations for each ligand to e.g. 500 (default is 100). This can be done using the Dock Ligands tool from the Toolbox, having the ligand in a Molecule Table (use the Extract Ligands tool to extract ligands from a Molecule Project and into a Molecule Tably).