THERE HAS BEEN GROWING INTERESTS OVER COMPUTATIONAL METHOD TO PREDICT THE ACTIVITIES OF NOVEL BIOCHEMICAL COMPOUNDS BEFORE SYNTHESIS. IN THIS RESPECT, QUANTITATIVE STRUCTUREACTIVITY RELATIONSHIP (QSAR) MODELS HAVE BEEN BUILT BY UTILIZING THE EXPERIMENTAL DATA [1]. USING SUCH AN APPROACH ONE COULD PREDICT THE ACTIVITIES OF NEWLY DESIGNED COMPOUNDS BEFORE A DECISION IS BEING MADE WHETHER THESE COMPOUNDS SHOULD BE REALLY SYNTHESIZED AND TESTED [1-2]. A linear QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR) MODEL IS PRESENTED FOR PREDICTING OF THE METALLOPROTEINASE INHIBITORY ACTIVITIES. A DATA SET CONTAINING 31, METALLOPROTEINASE INHIBITORS WITH KNOWN INHIBITORY ACTIVITIES WAS TAKEN AND USED FROM LITERATURE [3]. THE WHOLE DATA SET WAS DIVIDED INTO A TRAINING SET AND A TEST SET RANDOMLY. multiple linear regressions (MLR) WERE EMPLOYED TO MODEL THE RELATIONSHIPS BETWEEN MOLECULAR DESCRIPTORS AND BIOLOGICAL ACTIVITY OF MOLECULES USING THE STEPWISE (SW) METHOD AS VARIABLE SELECTION TOOL [4-5]. THE MLR MODEL GAVE SQUARED CORRELATION COEFFICIENT (R2) OF 0.887 AND SQUARED CROSS-VALIDATED CORRELATION COEFFICIENT (Q2 LOO) OF 0.811 FOR THE TRAINING SET COMPOUNDS. THE BUILT MODEL IS ALSO EVALUATED USING SERIES OF MOLECULES AS TEST SET. THE RESULTS OBTAINED FOR TEST SET (R2=0.955, F=7.93 AND RMSE=0.349) SHOWS THE GOOD PREDICTIVE ABILITY OF MODEL. THE PROPOSED MODEL HAS GOOD STABILITY, ROBUSTNESS AND PREDICTABILITY WHEN VERIFIED BY INTERNAL AND EXTERNAL VALIDATION. THE RESULTS INDICATE THAT THREE MOST RELEVANT DESCRIPTORS INCLUDING ATS5E, MATS4E AND MORE16M WITH THE CONTRIBUTION OF+66.63 (±12.96), +23.99 (±2.008) AND -1.352 (±0.4422), RESPECTIVELY PLAY A CRUCIAL ROLE IN ENHANCING THE INHIBITORY ACTIVITY. IT WAS CONCLUDED THAT BY INCREASING THE ELECTRONEGATIVITY CHARACTERISTIC OF THE MOLECULES AND ALSO DECREASING THE ATOMIC MASS OF THE MOLECULES, THE PIC50 VALUE AS THE INHIBITORY ACTIVITY FOR EACH MOLECULE WOULD BE INCREASE. THE RESULTS FROM THIS QSAR STUDY CAN GUIDE THE DESIGN OF NOVEL CONJUGATES WITH HIGHER METALLOPROTEINASE INHIBITOR ACTIVITY.