 |
PDBsum entry 2e4e
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
De novo protein
|
PDB id
|
|
|
|
2e4e
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Understanding the roles of amino acid residues in tertiary structure formation of chignolin by using molecular dynamics simulation.
|
|
|
Authors
|
|
T.Terada,
D.Satoh,
T.Mikawa,
Y.Ito,
K.Shimizu.
|
|
|
Ref.
|
|
Proteins, 2008,
73,
621-631.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
Abstract
|
|
|
Chignolin is a 10-residue peptide (GYDPETGTWG) that forms a stable beta-hairpin
structure in water. However, its design template, GPM12 (GYDDATKTFG), does not
have a specific structure. To clarify which amino acids give it the ability to
form the beta-hairpin structure, we calculated the folding free-energy
landscapes of chignolin, GPM12, and their chimeric peptides using multicanonical
molecular dynamics (MD) simulation. Cluster analysis of the conformational
ensembles revealed that the native structure of chignolin was the lowest in
terms of free energy while shallow local minima were widely distributed in the
free energy landscape of GPM12, in agreement with experimental observations.
Among the chimeric peptides, GPM12(D4P/K7G) stably formed the same beta-hairpin
structure as that of chignolin in the MD simulation. This was confirmed by
nuclear magnetic resonance (NMR) spectroscopy. A comparison of the free-energy
landscapes showed that the conformational distribution of the Asp3-Pro4 sequence
was inherently biased in a way that is advantageous both to forming hydrogen
bonds with another beta-strand and to initiating loop structure. In addition,
Gly7 helps stabilize the loop structure by having a left-handed alpha-helical
conformation. Such a conformation is necessary to complete the loop structure,
although it is not preferred by other amino acids. Our results suggest that the
consistency between the short-range interactions that determine the local
geometries and the long-range interactions that determine the global structure
is important for stable tertiary structure formation.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. (a) Superposition of chignolin MD structures from
cluster having largest population (pink) on representative NMR
structure (ivory). Each MD structure represents center of
subcluster with probability of existence larger than 1%. Only
non-hydrogen atoms of residues 2-9 are shown. (b) Close-up views
of residues 3-8 of MD structures from cluster having largest
population. Backbone non-hydrogen atoms and side-chain
non-hydrogen atoms of Asp3 are shown with stick model. Carbon,
nitrogen, and oxygen atoms are colored gray, blue, and red.
Hydrogen bonds are indicated with dotted lines.
|
|
Figure 7.
Figure 7. (a) Superposition of NMR structures of GPM12(D4P/K7G)
(green) on representative NMR structure of chignolin (ivory).
(b) Parts of NOESY and ROESY spectra of GPM12(D4P/K7G).
Crosspeaks of long-range NOEs characteristic of  -hairpin
structure are marked with red boxes.
|
|
|
|
|
|
The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2008,
73,
621-631)
copyright 2008.
|
|
|
|
|
|
|
|
Headers
|
|
|
|
|
|
