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SAMPLEX: automatic mapping of perturbed and unperturbed regions of proteins and complexes.

Krzeminski M, Loth K, Boelens R, Bonvin AM - BMC Bioinformatics (2010)

Bottom Line: Its performance is demonstrated for different applications including the prediction of disordered regions in partially unfolded proteins and of interacting regions in protein complexes.The proposed approach is suitable for partially unfolded states of proteins, local perturbations due to small ligands and protein-protein interfaces.The method is not restricted to NMR data, but is generic and can be applied to a wide variety of information.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, 3584 CH, Utrecht, The Netherlands.

ABSTRACT

Background: The activity of proteins within the cell is characterized by their motions, flexibility, interactions or even the particularly intriguing case of partially unfolded states. In the last two cases, a part of the protein is affected either by binding or unfolding and the detection of the respective perturbed and unperturbed region(s) is a fundamental part of the structural characterization of these states. This can be achieved by comparing experimental data of the same protein in two different states (bound/unbound, folded/unfolded). For instance, measurements of chemical shift perturbations (CSPs) from NMR 1H-15N HSQC experiments gives an excellent opportunity to discriminate both moieties.

Results: We describe an innovative, automatic and unbiased method to distinguish perturbed and unperturbed regions in a protein existing in two distinct states (folded/partially unfolded, bound/unbound). The SAMPLEX program takes as input a set of data and the corresponding three-dimensional structure and returns the confidence for each residue to be in a perturbed or unperturbed state. Its performance is demonstrated for different applications including the prediction of disordered regions in partially unfolded proteins and of interacting regions in protein complexes.

Conclusions: The proposed approach is suitable for partially unfolded states of proteins, local perturbations due to small ligands and protein-protein interfaces. The method is not restricted to NMR data, but is generic and can be applied to a wide variety of information.

Show MeSH
Selection of perturbed regions of CI2 after complexation with BPN'. In red and purple are displayed residues selected by SAMPLEX in a non-native like environment and in an ambiguous state, respectively. Spheres represent the interface based on the criterion defined in this paper: a residue belongs to the interface if at least one atom of the backbone is at a maximum distance of 5Å of any atom of the other subunit, excluding hydrogen atoms.
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Figure 2: Selection of perturbed regions of CI2 after complexation with BPN'. In red and purple are displayed residues selected by SAMPLEX in a non-native like environment and in an ambiguous state, respectively. Spheres represent the interface based on the criterion defined in this paper: a residue belongs to the interface if at least one atom of the backbone is at a maximum distance of 5Å of any atom of the other subunit, excluding hydrogen atoms.

Mentions: For CI2, SAMPLEX estimates that residues 56-62 are perturbed and residue 63 is in an ambiguous state. The CI2/BPN' X-ray complex, solved at 1.50 Å (PDB entry 1LW6) [8], shows that residues 50 and 54 to 61 are involved in the interaction (Figure 2). Residue 50 however is only defined as interacting based on the proximity of its carbonyl oxygen to a side chain oxygen of D99 in BPN' (distance between both oxygens is 4.8 Å). This can explain why its amide group is not affected by the binding and therefore not selected by SAMPLEX.


SAMPLEX: automatic mapping of perturbed and unperturbed regions of proteins and complexes.

Krzeminski M, Loth K, Boelens R, Bonvin AM - BMC Bioinformatics (2010)

Selection of perturbed regions of CI2 after complexation with BPN'. In red and purple are displayed residues selected by SAMPLEX in a non-native like environment and in an ambiguous state, respectively. Spheres represent the interface based on the criterion defined in this paper: a residue belongs to the interface if at least one atom of the backbone is at a maximum distance of 5Å of any atom of the other subunit, excluding hydrogen atoms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823710&req=5

Figure 2: Selection of perturbed regions of CI2 after complexation with BPN'. In red and purple are displayed residues selected by SAMPLEX in a non-native like environment and in an ambiguous state, respectively. Spheres represent the interface based on the criterion defined in this paper: a residue belongs to the interface if at least one atom of the backbone is at a maximum distance of 5Å of any atom of the other subunit, excluding hydrogen atoms.
Mentions: For CI2, SAMPLEX estimates that residues 56-62 are perturbed and residue 63 is in an ambiguous state. The CI2/BPN' X-ray complex, solved at 1.50 Å (PDB entry 1LW6) [8], shows that residues 50 and 54 to 61 are involved in the interaction (Figure 2). Residue 50 however is only defined as interacting based on the proximity of its carbonyl oxygen to a side chain oxygen of D99 in BPN' (distance between both oxygens is 4.8 Å). This can explain why its amide group is not affected by the binding and therefore not selected by SAMPLEX.

Bottom Line: Its performance is demonstrated for different applications including the prediction of disordered regions in partially unfolded proteins and of interacting regions in protein complexes.The proposed approach is suitable for partially unfolded states of proteins, local perturbations due to small ligands and protein-protein interfaces.The method is not restricted to NMR data, but is generic and can be applied to a wide variety of information.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, 3584 CH, Utrecht, The Netherlands.

ABSTRACT

Background: The activity of proteins within the cell is characterized by their motions, flexibility, interactions or even the particularly intriguing case of partially unfolded states. In the last two cases, a part of the protein is affected either by binding or unfolding and the detection of the respective perturbed and unperturbed region(s) is a fundamental part of the structural characterization of these states. This can be achieved by comparing experimental data of the same protein in two different states (bound/unbound, folded/unfolded). For instance, measurements of chemical shift perturbations (CSPs) from NMR 1H-15N HSQC experiments gives an excellent opportunity to discriminate both moieties.

Results: We describe an innovative, automatic and unbiased method to distinguish perturbed and unperturbed regions in a protein existing in two distinct states (folded/partially unfolded, bound/unbound). The SAMPLEX program takes as input a set of data and the corresponding three-dimensional structure and returns the confidence for each residue to be in a perturbed or unperturbed state. Its performance is demonstrated for different applications including the prediction of disordered regions in partially unfolded proteins and of interacting regions in protein complexes.

Conclusions: The proposed approach is suitable for partially unfolded states of proteins, local perturbations due to small ligands and protein-protein interfaces. The method is not restricted to NMR data, but is generic and can be applied to a wide variety of information.

Show MeSH