PDBsum entry 2e4e

De novo protein

PDB id: 2e4e

Contents

Ligands

GLY-TYR-ASP-PRO-ALA-THR-GLY-THR-PHE-GLY

PDB id:

2e4e

Name:

De novo protein

Title:

Nmr structure of d4p/k7g mutant of gpm12

Structure:

Gpm12. Chain: a. Synonym: chignolin. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Other_details: chemical peptide synthesis

NMR struc:

23 models

Authors:

T.Terada,D.Satoh,T.Mikawa,Y.Ito,K.Shimizu

Key ref:

T.Terada et al. (2008). Understanding the roles of amino acid residues in tertiary structure formation of chignolin by using molecular dynamics simulation. Proteins, 73, 621-631. PubMed id: 18473359 DOI: 10.1002/prot.22100

Date:

06-Dec-06 Release date: 05-Feb-08

DOI no: 10.1002/prot.22100

Proteins 73:621-631 (2008)

PubMed id: 18473359

Understanding the roles of amino acid residues in tertiary structure formation of chignolin by using molecular dynamics simulation.

T.Terada, D.Satoh, T.Mikawa, Y.Ito, K.Shimizu.

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.

Selected figure(s)

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.

Figures were selected by the author.

Author's comment

The tertiary structure of GPM12(D4P/K7G) was determined to confirm the prediction from molecular dynamics simulation that it stably forms β-hairpin as does chignolin.
Tohru Terada