PRELUDE & FUGUE
predict the local structure of a protein in
terms of backbone dihedral angle domains, identify sequence regions that form early during
folding, and locate structural weaknesses, defined as regions whose sequence
is not optimal with respect to the tertiary fold.
These programs use a statistical backbone torsion angle potential, which describes
local interactions along the chain and is derived from a set of 1403 known protein structures.
The input they require is the amino acid sequence of the target protein.
The output yields the predicted structures given in terms of 7 backbone torsion angle
assignments noted A, B, C, G, E, O, P; the phi, psi, and omega values associated to these assignments are given here
Using Prelude&Fugue as a 2D structure prediction method
For an assessment of the performances, click here
Using Prelude&Fugue to determine peptides that adopt a preferred
conformation in solution
For an example where Prelude
were used to propose sequences of
helical peptides, which were synthesized and shown by CD and NMR to be indeed helical in a mixture of
water and TFE at room temperature, see:
Conformational properties of four peptides corresponding to alpha-helical
regions of Rhodospirillum cytochrome c2 and bovine calcium binding protein.
Pintar A, Chollet A, Bradshaw C, Chaffotte A, Cadieux C, Rooman MJ, Hallenga
K, Knowles J, Goldberg M, Wodak SJ.
Biochemistry. 1994 Sep 20;33(37):11158-73.
Using Prelude&Fugue to identify early folding regions
For an analysis of the conservation of segments predicted to have well defined
instrinsic structural preferences in families
of homologous regions, and for a comparison with experimental data on early
folding intermediates, see:
Extracting information on folding from the amino acid sequence: consensus
regions with preferred conformation in homologous proteins.
Rooman MJ, Wodak SJ.
Biochemistry. 1992 Oct 27;31(42):10239-49.
Using Prelude&Fugue to identify structural weaknesses
have been applied to proteins known to adopt alternative
structures that provoke conformational diseases or correspond to 3D domain swapping.
In these proteins, sequence regions have been detected whose intrinsic preferred conformations
differ from the native conformation, and could represent
structural weaknesses that facilitate misfolding. For an application to the amylodoigenic prion proteins, see :
PoPMuSiC, an algorithm for predicting protein mutant stability changes:
application to prion proteins.
Gilis D, Rooman M.
Protein Eng. 2000 Dec;13(12):849-56.
For an application to proteins that undergo 3D domain swapping, see :
Sequence-structure signals of 3D domain swapping in proteins.
Dehouck Y, Biot C, Gilis D, Kwasigroch JM, Rooman M.
J Mol Biol. 2003 Jul 25;330(5):1215-25.