Another interesting observation from our simulations is that LZE binding at site B1 prevents this rotation of domain III. In order to understand this behaviour, we compared the last frame of replica 9 (with domain III rotated) with the last frame of replica 7 (no rotation). Figure (left panel) displays the comparison of these two conformations (replica 9 in orange and replica 7 in cyan). ARG298 and MET6 are also shown for replica 7 and it is clear that they too far apart to form a hydrogen bond. Nevertheless, domain III does not rotate at all in replica 7 unlike replica 9. The proposed explanation here is that the binding of LZE at site B1 (shown as a surface in Figure