The flexibility and dynamics of protein disulfide isomerase

Rudolf A. Römer, Stephen A. Wells, J. Emilio Jimenez-Roldan, Moitrayee Bhattacharyya, Saraswathi Vishweshwara, Robert B. Freedman

Research output: Contribution to journalArticlepeer-review

18 Citations (SciVal)


We have studied the mobility of the multidomain folding catalyst, protein disulfide isomerase (PDI), by a coarse-graining approach based on flexibility. We analyze our simulations of yeast PDI (yPDI) using measures of backbone movement, relative positions and orientations of domains, and distances between functional sites. We find that there is interdomain flexibility at every interdomain junction but these show very different characteristics. The extent of interdomain flexibility is such that yPDI's two active sites can approach much more closely than is found in crystal structures—and indeed hinge motion to bring these sites into proximity is the lowest energy normal mode of motion of the protein. The flexibility predicted for yPDI (based on one structure) includes the other known conformation of yPDI and is consistent with (i) the mobility observed experimentally for mammalian PDI and (ii) molecular dynamics. We also observe intradomain flexibility and clear differences between the domains in their propensity for internal motion. Our results suggest that PDI flexibility enables it to interact with many different partner molecules of widely different sizes and shapes, and highlights considerable similarities of yPDI and mammalian PDI. Proteins 2016; 84:1776–1785.

Original languageEnglish
Pages (from-to)1776-1785
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Issue number12
Publication statusPublished - 1 Dec 2016


  • and computer simulation
  • dynamics of biomolecules
  • large-domain motion
  • modeling
  • PDI
  • protein dynamics
  • protein flexibility
  • theory

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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