Violation in number of HBD, HBA, molecular weight, and LogP were detected. As an additional validation setup, all the four identified lead compounds were 4F 4PP oxalate mapped onto the structure-based pharmacophore. The mapping pattern was observed to augment the confidence in identified novel lead structures. The comparison of pharmacophoric features obtained from structure-based and ligand-based study revealed that both the pharmacophores have four common points i.e. two hydrogen bond acceptors and two hydrophobic groups. The 5-OMe-UDP trisodium salt pharmacophore obtained from structure-based study exhibited one additional feature i.e. hydrogen bond donors. This observation revealed that along with HBA and HY features, HBD feature can also contribute an additional interaction site at HIV-1 protease. All the 47 compounds of the compound library were mapped onto the generated structure-based pharmacophore. One of the interesting outcome of the study was that out of different conformations of 47 compounds, 351 hits were obtained and 41 hits exhibited a five-feature mapping and rest all showed a four-feature interaction. These hits presented the chemical features and the shape suggested by the structure-based pharmacophore model. Mapping fashion of least active compound 8t onto the structure-based pharmacophore was also analyzed, which exhibited a four-feature fit in which hydrogen bond acceptor was missing due to absence of cyclic urea carbonyl group and hence resulted in least biological activity. Interestingly, comparison of pharmacophoric interactions of both the pharmacophores display common binding mode and indicates the significance of hydrogen bond acceptor, donor and hydrophobic functionalities in defining the activities of compounds. It is also interesting to note that the seventeen different conformations of the compound 9s were obtained as hits, out of seventeen conformations sixteen mapped to four features of the input pharmacophore whereas one mapped to five features, i.e. two hydrogen bond acceptors, two hydrophobes and one hydrogen bond donor. It seems that one out of seventeen different conformers is able to adopt a orientation which can interact with all five pharmacophoric features at HIV-1 protease binding pocket due to conformational adjustment. Hence, the model developed herein also highlights the importance of bioactive conformation in eliciting the biological response.