HIV-1 reverse transcriptase (RT) is one of the key targets for anti-AIDS chemotherapy which is responsible for the conversion of the single-stranded RNA of HIV-1 into double-stranded DNA. The non-nucleoside RT inhibitors (NNRTIs) such as nevirapine, binds in a hydrophobic pocket, induced conformational change of the enzyme. We have performed two conventional molecular dynamics simulations of mutant Y181C HIV-1RT and the complex with nevirapine for 1 ns at 300 K. These two systems are an ideal target for elucidate the conformational change of the binding pocket and the binding affinity between mutant RT and nevirapine. The simulations show that the free RT trajectories have larger fluctuations than co, plex RT/nevirapine, particularly, the p66 fingers and palm subdomains. Glu138 in the finger subdo in and Ile180 in the binding pocket are proposed to be effected by nevirapine. The inhibitor shows flu tuation in two conformational states which was caused by the flexibility of cyclopropyl group. These induce Cys181 and Lys102 to be lower flexibility and Lys101, Phe227, Trp229 to be higher flexibility. Nevirapine also affects to the flexibility of active aspartic triad residues, Asp 110 and Asp 185, a cept Asp 186. One H-bonding interaction was observed between the binding pocket residues Cys181 and N1 in ring A of nevirapine. One significant crystal water molecule forms water-bridged H-bonding interaction between nevirapine and Leu234 and His235, to stabilize the complex. The H-bo ding between crystal water mol ecules and binding residues in the free RT enzyme was not observed. The equilibrium structure of the free RT enzyme is staying in openstructure which C(+,a) distance b tween the finger tip, Trp24, and thumb tip, Ala288, is about 39.87 (...) corresponding to the crystallo aphic structure code 1JLE. The C(+,a) pocket entrance distance between Leu100 and Va1179 opens idely in complex RT. Comparison between free RT simulations structure and crystallographic code 1JLE shows rmsd 1.59 (...). Comparison between complex RT/nevira pine simulation structure and crystallographic code 1JLB shows rmsd 1.59 (...). Taken into account, the equilibrium enzyme structures as obtained from MD simulations can be reliable. Moreover, the obtained results can b used to get more understanding of the drug-enzyme interactions which will be helpful for the desi n of new higher potent inhibitor active against mutant HIV-1 RT.