Journal of Biomolecular NMR

, Volume 31, Issue 1, pp 59–64 | Cite as

Generation of native-like protein structures from limited NMR data, modern force fields and advanced conformational sampling

  • Jianhan Chen
  • Hyung-Sik Won
  • Wonpil Im
  • H. Jane Dyson
  • Charles L. BrooksIII


Determining an accurate initial native-like protein fold is one of the most important and time-consuming steps of de novo NMR structure determination. Here we demonstrate that high-quality native-like models can be rapidly generated from initial structures obtained using limited NOE assignments, through replica exchange molecular dynamics refinement with a generalized Born implicit solvent (REX/GB). Conventional structure calculations using an initial sparse NOE set were unable to identify a unique topology for the zinc-bound C-terminal domain of E. coli chaperone Hsp33, due to a lack of unambiguous long range NOEs. An accurate overall topology was eventually obtained through laborious hand identification of long range NOEs. However we were able to obtain high-quality models with backbone RMSD values of about 2 Å with respect to the final structures, using REX/GB refinement with the original limited set of initial NOE restraints. These models could then be used to make further assignments of ambiguous NOEs and thereby speed up the structure determination process. The ability to calculate accurate starting structures from the limited unambiguous NOE set available at the beginning of a structure calculation offers the potential of a much more rapid and automated process for NMR structure determination.


generalized born implicit solvent NOE assignment replica exchange structure determination structure refinement 



generalized born with a simple switching function


nuclear magnetic resonance


nuclear overhauser effect


nuclear overhauser enhanced spectroscopy


replica exchange




root-mean-square deviation


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Supplementary material

10858_2004_Article_6056_MOESM1_ESM.pdf (108 kb)
Supplementary material (PDF 109 KB)


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Copyright information

© Springer 2005

Authors and Affiliations

  • Jianhan Chen
    • 1
  • Hyung-Sik Won
    • 1
  • Wonpil Im
    • 1
  • H. Jane Dyson
    • 1
  • Charles L. BrooksIII
    • 1
  1. 1.Department of Molecular BiologyThe Scripps Research InstituteLaJollaU.S.A.

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