  We have studied the mobility of the folding catalyst, protein
disulphide-isomerase (PDI), by molecular dynamics and by a rapid approach based
on flexibility. We analysed our simulations using measures of backbone
movement, relative positions and orientations of domains, and distances between
functional sites. Despite their different assumptions, the two methods are
surprisingly consistent. Both methods agree that motion of domains is dominated
by hinge and rotation motion of the a and a' domains relative to the central
b-b' domain core. We identify the a' domain as showing the greatest
intra-domain mobility. The flexibility method, which requires 10^4-fold less
computer power, predicts additional large-scale features of inter-domain motion
that have been observed experimentally. We conclude that the methods offer
complementary insight into the motion of this large protein and provide
detailed structural models that characterise its functionally-significant
conformational changes.
