||We are working towards the understanding of protein-protein interaction between HIV-1 integrase and human Lens epithelium-derived growth factor (LEDGF/p75) through mutational studies and molecular dynamics simulations. HIV-1 integrase has emerged as a promising target as this is responsible for integration of the newly synthesized double-stranded viral DNA into host genomic DNA. HIV-1 integrase strand transfer inhibitors, which target the enzyme active site have witnessed clinical success over past few years, but the emergence of drug resistance poses challenges. HIV relies on host cellular machinery to complete its replication cycle. Cellular cofactors are important for integration function of integrase. The host cell cofactor LEDGF/p75 plays an important role in the integration process by tethering IN to chromatin. Crystal structure of the dimeric CCD of HIV-1 integrase complexed to the integrase binding domain (IBD) of LEDGF/p75 gave a major advance for structure-based drug design targeting the IN-LEDGF/p75 protein-protein interaction.