10.22376/ijpbs.2019.10.1.p1-12 Volume 3 Issue 4 2012(October - December) Fosmidomycin and its derivatives belong to class DOX-reductoisomerase (DXR) inhibitors. A fosmidomycin analogues library was designed with 43 analogues, their molecular interactions and binding affinities with DXR (PDB ID: 1ONP) have been studied using Glide docking, QM-polarized ligand docking (QPLD), molecular mechanics based on generalized Born/surface area (MM-GB/SA) and multi-ligand bimolecular association with energetics (eMBrAcE). Prediction models were developed between DXR inhibition activity (pIC lessThan sub greaterThan 50 lessThan /sub greaterThan ) of these compounds and molecular descriptors like Glide score, QPLD lessThan sub greaterThan score lessThan /sub greaterThan , binding energy and calculated free energy of binding. The lessThan i greaterThan r lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan /i greaterThan lessThan sup greaterThan lessThan /sup greaterThan value ranges from 0.608-0.807 indicating good data fit, and lessThan i greaterThan r lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan sub greaterThan cv lessThan /sub greaterThan lessThan /i greaterThan ranges from 0.592-0.799 indicating acceptable predictive capabilities of models. Linear correlation between predicted and experimented pIC lessThan sub greaterThan 50 lessThan /sub greaterThan was observed ( lessThan i greaterThan r lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan /i greaterThan = 0.603-0.781). Low root mean square error (0.39-0.84) of inhibitors was established in all structure-centric approaches, an efficient tool for generating potential and specific inhibitors of DXR by testing rationally designed lead compounds based on fosmidomycin derivatization. AMIYA KUMAR PATEL DOX-reductoisomerase, Fosmidomycin, Docking and scoring, Virtual screening, Drug discovery. 72-91