Molecular docking is a key tool for studying protein-ligand or protein-protein interactions and for designing new drugs. Majority of the current binding/docking methods attempt to predict the bound ligand by keeping the protein (receptor) fixed and moving the target ligand around the binding site while performing an energy minimization. Modeling of protein binding site flexibility is still a challenging problem due to the large conformational space that must be sampled and inaccurate energy function.Here, we discuss a new strategy for achieving successful flexible docking of peptides to PDZ domains. Due to promiscuous behavior of PDZ domain proteins, two different sets of conformations are obtained by perturbing the unbound structure along the normal modes of elastic network model (ENM) responsible for Class I and Class II type binding. A restrained replica exchange molecular dynamics (REMD) is applied to these perturbed structures to explore the conformational space of the protein receptor. After restrained-REMD, different peptides are docked to each individual snapshots of the receptor to generate a collection of docked complexes of different stabilities.