Amino acids at 271 and 274 are relatively conserved and big side chains may be important in maintaining RT stability and resistance to proteolysis By comparing 1083 complete sequences of HIV-1, it was found that the amino acids at 271 and 274 were relatively conserved. As shown in Table 2 , tyrosine (Y) is the predominant naturally existent amino acid at 271 residue (99.19%), while phenylalanine (F), histidine (H) and cysteine (C) occur rarely (,1%). Similarly, isoleucine (I) is the predominant naturally existent amino acid at 274, which accounts for 98.43%, while in less than 2% of all cases, valine (V) and leucine (L) are found at this site. This finding suggested that these amino acids might probably play important role in maintaining the active conformation of RT. Consistently, structural analysis suggested that amino acids at these two sites are buried in the thumb region of RT (Fig. 6A) . It was further revealed that all wild type RTs have relatively big side chains, but they are absent from the mutants 271A and 274A (Fig. 6B & 6C) . Thus, the loss of the side chains in the RT mutants plausibly leads to conformational change of RT, leading to aberrance in dimer formation and susceptibility to proteolysis by HIV-1 protease.