The identification and characterization of binding sites is a critical component of structure-based drug design (SBDD). Probe-based/cosolvent molecular dynamics (MD) methods that allow for protein flexibility have been developed to predict ligand binding sites. However, cryptic pockets that appear only upon ligand binding and occluded binding sites with no access to the solvent pose significant challenges to these methods. Here, we report the development of accelerated ligand-mapping MD (aLMMD), which combines accelerated MD with LMMD, for the detection of these challenging binding sites. The method was validated on five proteins with what we term "recalcitrant" cryptic pockets, which are deeply buried pockets that require extensive movement of the protein backbone to expose, and three proteins with occluded binding sites. In all the cases, aLMMD was able to detect and sample the binding sites. Our results suggest that aLMMD could be used as a general approach for the detection of such elusive binding sites in protein targets, thus providing valuable information for SBDD.