The association between the MEEVD C-terminal peptide from the heat shock protein 90 (Hsp90) and tetratricopeptide repeat A (TPR2A) domain of the heat shock organizing protein (Hop) is a useful prototype to study the fundamental molecular details about the Hop-Hsp90 interaction. We study here the mechanism of binding/unbinding and compute the standard binding free energy and potential of mean force for the association of the MEEVD peptide to the TPR2A domain using the Adaptive Biasing Force (ABF) methodology. We observe conformational changes of the peptide and the protein receptor induced by binding. We measure the binding free energy of -8.4 kcal/mol, which is consistent with experimental estimates. The simulations achieve multiple unbinding and rebinding events along a consistent pathway connecting the binding site to solvent. The MEEVD peptide slowly dissociates disrupting the hydrogen bonds first, then tilting on the side while preserving the interaction with the side chain of residue Asp 5 of the peptide. After this initial displacement, the peptide completely dissociates and moves into the solvent. Rebinding of the MEEVD peptide from the solvent to the receptor binding site occurs slowly through the portal of entry. Unbinding and rebinding go through intermediate states characterized by the peptide interacting with a lateral helix, helix A1, of the receptor with mainly Asp 5, Val 4, and Glu 3 of the peptide. This newly discovered intermediate structure is characterized by numerous contacts with the receptor which lead to complete formation of the bound complex. The structure of the bound complex obtained after rebinding is structurally very similar to the crystal structure of the complex (0.48 Å root-mean square deviation). The residues Asp 5, Val 4, and Glu 3 adopt conformations and intermolecular contacts with excellent structural similarity with the native ones. Finally, the dissociation and reassociation of MEEVD induce hydration/dehydration transitions, which provide insights on the role of desolvation and solvation processes in protein-peptide binding.