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PDBsum entry 1kd8
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De novo protein
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PDB id
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1kd8
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Side-Chain repacking calculations for predicting structures and stabilities of heterodimeric coiled coils.
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Authors
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A.E.Keating,
V.N.Malashkevich,
B.Tidor,
P.S.Kim.
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Ref.
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Proc Natl Acad Sci U S A, 2001,
98,
14825-14830.
[DOI no: ]
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PubMed id
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Abstract
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An important goal in biology is to predict from sequence data the
high-resolution structures of proteins and the interactions that occur between
them. In this paper, we describe a computational approach that can make these
types of predictions for a series of coiled-coil dimers. Our method comprises a
dual strategy that augments extensive conformational sampling with molecular
mechanics minimization. To test the performance of the method, we designed six
heterodimeric coiled coils with a range of stabilities and solved x-ray crystal
structures for three of them. The stabilities and structures predicted by the
calculations agree very well with experimental data: the average error in
unfolding free energies is <1 kcal/mol, and nonhydrogen atoms in the
predicted structures superimpose onto the experimental structures with rms
deviations <0.7 A. We have also tested the method on a series of homodimers
derived from vitellogenin-binding protein. The predicted relative stabilities of
the homodimers show excellent agreement with previously published experimental
measurements. A critical step in our procedure is to use energy minimization to
relax side-chain geometries initially selected from a rotamer library. Our
results show that computational methods can predict interaction specificities
that are in good agreement with experimental data.
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Figure 1.
Fig. 1. Helical wheel diagram of the heterodimeric coiled
coil GABH. Substitutions of Val, Ile, and Leu were made at
positions d12 and a16 (yellow boxes) to give six peptides:
A[LI]B[LL], A[LL]B[LL], A[IV]B[LL], A[LL]B[IV], A[LI]B[IV], and
A[IV]B[IV] (notation: Acid[d12a16]Base[d12a16]). The linear
sequence is:
Ac-(E/K)VKQL(E/K)A(E/K)VEEd12(E/K)S(E/K)a16WHL(E/K)N(E/K)VARL(E/K)K(E/K)NAEC(E/K)A-NH[2];
the ACID peptide has E and the BASE peptide has K at positions
in parentheses.
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Figure 6.
Fig. 6. Superposition of the x-ray and
MIN-FULL-calculated structures. The structures shown correspond
to the first entries in Table 3 for each peptide. The view is
from the C terminus of the peptide and includes positions a16
and d12.
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