 |
PDBsum entry 1fsd
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Novel sequence
|
PDB id
|
|
|
|
1fsd
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
De novo protein design: fully automated sequence selection.
|
|
|
Authors
|
|
B.I.Dahiyat,
S.L.Mayo.
|
|
|
Ref.
|
|
Science, 1997,
278,
82-87.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The first fully automated design and experimental validation of a novel sequence
for an entire protein is described. A computational design algorithm based on
physical chemical potential functions and stereochemical constraints was used to
screen a combinatorial library of 1.9 x 10(27) possible amino acid sequences for
compatibility with the design target, a betabetaalpha protein motif based on the
polypeptide backbone structure of a zinc finger domain. A BLAST search shows
that the designed sequence, full sequence design 1 (FSD-1), has very low
identity to any known protein sequence. The solution structure of FSD-1 was
solved by nuclear magnetic resonance spectroscopy and indicates that FSD-1 forms
a compact well-ordered structure, which is in excellent agreement with the
design target structure. This result demonstrates that computational methods can
perform the immense combinatorial search required for protein design, and it
suggests that an unbiased and quantitative algorithm can be used in various
structural contexts.
|
|
|
|
|
|
|
|
Figure 2.
Fig. 2. Comparison of Zif268 (9) and computed FSD-1
structures. (A) Stereoview of the second zinc finger module of
Zif268^ showing its buried residues and zinc binding site. (B)
Stereoview of the computed orientations of buried side chains in
FSD-1. For clarity, only side chains from residues 3, 5, 8, 12,
18, 21, 22, and 25 are shown. Color figures were created with
MOLMOL (38).
|
|
Figure 6.
Fig. 6. Comparison of the FSD-1 structure (blue) and the
design target (red). Stereoview of the best-fit superposition of
the restrained^ energy minimized average NMR structure of FSD-1
and the backbone^ of Zif268. Residues 3 to 26 are shown.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
278,
82-87)
copyright 1997.
|
|
|
|
|
|
|
