Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm

J Mol Biol. 1993 Dec 5;234(3):826-36. doi: 10.1006/jmbi.1993.1628.


The F-actin model has been refined by a Directed Mutation Algorithm, a reiterative procedure which combines a Monte-Carlo method of selecting subdomains to be refined at each cycle with a non-linear least-squares routine to get the best fit for the particular selected domains. The G-actin crystal structure was used as a starting model. The experimental data were obtained by X-ray fiber diffraction patterns from oriented F-actin gels. After 250 cycles we were able to obtain an almost perfect fit of the calculated diffraction pattern to the experimental diffraction pattern as well as a reasonable stereochemistry including intermolecular interactions of the actin monomers with an r.m.s. shift in the C alpha-positions of 3.2 A from the crystal coordinates. The stereochemistry of the intersubunit packing was calculated by molecular dynamics using the program X-PLOR. In addition, the binding site of phalloidin, a cyclic heptapeptide from the mushroom Amanita phalloides, could be determined. Furthermore, we were able to determine differences in the structures of F-actin with and without phalloidin. The method proved itself robust and showed a high degree of convergence.

MeSH terms

  • Actins / chemistry*
  • Algorithms
  • Amino Acid Sequence
  • Mathematics
  • Models, Molecular
  • Molecular Sequence Data
  • Monte Carlo Method
  • Mutagenesis, Site-Directed*
  • Phalloidine
  • Protein Structure, Secondary*
  • Recombinant Proteins / chemistry
  • X-Ray Diffraction / methods


  • Actins
  • Recombinant Proteins
  • Phalloidine