Anti-retroviral therapies for acquired immunodeficiency syndrome (AIDS) patients are at risk because of drug resistance that has been identified with a number of currently marketed drugs. HIV-1 protease (HIV-pr), a well-validated AIDS therapeutic target, undergoes various mutations leading to resistance such existing drugs. However, the molecular basis of drug resistance of HIV-pr is still not fully understood. JE-2147, an experimental inhibitor of HIV-pr, shows a resistance profile different from that of known drugs. Noteworthy, it is less susceptible to several common mutations, but it is still susceptible to a few mutations, including I47V which appears to be specific for JE-2147. In this work, the molecular details of the effect of I47V mutation is investigated using molecular dynamics simulation. Four simulations of apo and complexed proteins in their wild type (WT) and mutant forms have been performed. It is found that the mobility of the side chain of mutant Val47 in chain B of HIV-pr about the inhibitor increases significantly relative to WT Ile47 in chain B. This is due to loss of optimized packing of the inhibitor to the residue 47 in chain B of the mutant when compared with WT enzyme. There also are subtle differences in motion involving residues in the flap region, which are more prominent in the apo form.