The human p97 enzyme is a member of the ATPase family which participates in several biological processes. This protein with the help of cofactors extracts the misfolded target substrate from membranes or stable protein assemblies through the hydrolysis of ATP. However, the mechanism of substrate processing via human p97 ATPase in complex with a different types of cofactors remains poorly understood. Hence, this project aims to understand the protein-protein interaction of p97 in complex with its cofactors through both bioinformatics analysis and wet-lab experiments and determine the impact of each cofactor on conformational changes of p97 during the ATPase cycle.