Folding of small helical proteins assisted by small-angle X-ray scattering profiles

Structure. 2005 Nov;13(11):1587-97. doi: 10.1016/j.str.2005.07.023.


This paper reports a computational method for folding small helical proteins. The goal was to determine the overall topology of proteins given secondary structure assignment on sequence. In doing so, a Monte Carlo protocol, which combines coarse-grained normal modes and a Hamiltonian at a different scale, was developed to enhance sampling. In addition to the knowledge-based potential functions, a small-angle X-ray scattering (SAXS) profile was also used as a weak constraint for guiding the folding. The algorithm can deliver structural models with overall correct topology, which makes them similar to those of 5 approximately 6 A cryo-EM density maps. The success could contribute to make the SAXS technique a fast and inexpensive solution-phase experimental method for determining the overall topology of small, soluble, but noncrystallizable, helical proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology*
  • Models, Molecular
  • Monte Carlo Method
  • Protein Folding*
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Scattering, Radiation
  • X-Ray Diffraction
  • X-Rays


  • Proteins