The dynamics and flexibility of protein disulphide-isomerase (PDI): predictions of experimentally-observed domain motions

Abstract

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.

20 pages text, 5 figures, and full supplemental information

References in corpus (3)

• Rapid simulation of protein motion: merging flexibility, rigidity and normal mode analyses
• Characterizing the folding core of the cyclophilin A - cyclosporin A complex I: hydrogen exchange data and rigidity analysis
• Characterizing the folding core of the cyclophilin A - cyclosporin A complex II: improving folding core predictions by including mobility