Folate receptor is one of the possible targets for anticancer drugs, and this observation is supported by the current use of antifolates in various cancer therapies. In the process of folic acid consumption by a cell, the receptor goes through various stages of endocytosis with changing pH. Moreover, it is known that tumor cells have a more acidic pH than normal cells. However, the pH dependence binding and release of folate and its difference from antifolates is not well understood at this moment. Furthermore, identification of key amino acid residues within folate receptors responsible for the pH-dependent conformational changes observed within the apo and holo-structures of folate receptors will further an effort to design new antifolates with specific properties. Here, we study pKa shifts of amino acids at different stages using Constant pH Molecular Dynamics and their effect on different molecule uptake by the folate receptor.