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Characterization of non-trivial neighborhood fold constraints from protein sequences using generalized topohydrophobicity.

Fourty G, Callebaut I, Mornon JP - Bioinform Biol Insights (2008)

Bottom Line: From a large set of structural alignments processed from the FSSP database, we selected 1485 structural sub-families including at least 8 members, with accurate alignments and limited redundancy.We show that residues within helices, even when deeply buried, have few non-trivial neighbors (0-2), whereas beta-strand residues clearly exhibit a multimodal behavior, dominated by the local geometry of the tetrahedron (3 non-trivial close neighbors associated with one tetrahedron; 6 with two tetrahedra).Useful topological constraints on the immediate neighborhood of an amino acid, but also on its correlated solvent accessibility, can thus be derived using this approach, from the simple knowledge of multiple sequence alignments.

View Article: PubMed Central - PubMed

Affiliation: Département de Biologie Structurale, Institut de Minéralogie et de Physique des Milieux Condensés, CNRS UMR 7590 - Universités Paris 6/Paris 7, France.

ABSTRACT
Prediction of key features of protein structures, such as secondary structure, solvent accessibility and number of contacts between residues, provides useful structural constraints for comparative modeling, fold recognition, ab-initio fold prediction and detection of remote relationships. In this study, we aim at characterizing the number of non-trivial close neighbors, or long-range contacts of a residue, as a function of its "topohydrophobic" index deduced from multiple sequence alignments and of the secondary structure in which it is embedded. The "topohydrophobic" index is calculated using a two-class distribution of amino acids, based on their mean atom depths. From a large set of structural alignments processed from the FSSP database, we selected 1485 structural sub-families including at least 8 members, with accurate alignments and limited redundancy. We show that residues within helices, even when deeply buried, have few non-trivial neighbors (0-2), whereas beta-strand residues clearly exhibit a multimodal behavior, dominated by the local geometry of the tetrahedron (3 non-trivial close neighbors associated with one tetrahedron; 6 with two tetrahedra). This observed behavior allows the distinction, from sequence profiles, between edge and central beta-strands within beta-sheets. Useful topological constraints on the immediate neighborhood of an amino acid, but also on its correlated solvent accessibility, can thus be derived using this approach, from the simple knowledge of multiple sequence alignments.

No MeSH data available.


Prediction of relative solvent accessibility. Evolution of the level of good predictions (dotted line) and of the fraction of predicted residues (solid line) as a function of the secondary structure conservation.
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f14-bbi-2008-047: Prediction of relative solvent accessibility. Evolution of the level of good predictions (dotted line) and of the fraction of predicted residues (solid line) as a function of the secondary structure conservation.

Mentions: Influence of the major secondary structure threshold on prediction. We fixed the minimal work position occupancy at 8 and let the major secondarystaterangefrom33%to100%. Figure S3 shows the link between these parameters and confirms that a level of 75% for the major secondary structure threshold constitutes an acceptable compromise for a large-scale study. When work position occupancy and major secondary structure conservation are high, predictions are better but remain applicable to a reduced set of work positions. The couple (1, 33 %) leads to 74% of good predictions for 100% of H or E positions. In contrast, (35, 95%) leads to 87 % of good predictions but only for 3% of H or E positions. (8, 75%) and (10, 80%) give 77% and 79% of good predictions, respectively, for 40% and 27% of H or E positions. All these predictions are performed through a 10-fold cross-validation procedure on the whole bank of 16 000 residues occupying a work position.


Characterization of non-trivial neighborhood fold constraints from protein sequences using generalized topohydrophobicity.

Fourty G, Callebaut I, Mornon JP - Bioinform Biol Insights (2008)

Prediction of relative solvent accessibility. Evolution of the level of good predictions (dotted line) and of the fraction of predicted residues (solid line) as a function of the secondary structure conservation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2735972&req=5

f14-bbi-2008-047: Prediction of relative solvent accessibility. Evolution of the level of good predictions (dotted line) and of the fraction of predicted residues (solid line) as a function of the secondary structure conservation.
Mentions: Influence of the major secondary structure threshold on prediction. We fixed the minimal work position occupancy at 8 and let the major secondarystaterangefrom33%to100%. Figure S3 shows the link between these parameters and confirms that a level of 75% for the major secondary structure threshold constitutes an acceptable compromise for a large-scale study. When work position occupancy and major secondary structure conservation are high, predictions are better but remain applicable to a reduced set of work positions. The couple (1, 33 %) leads to 74% of good predictions for 100% of H or E positions. In contrast, (35, 95%) leads to 87 % of good predictions but only for 3% of H or E positions. (8, 75%) and (10, 80%) give 77% and 79% of good predictions, respectively, for 40% and 27% of H or E positions. All these predictions are performed through a 10-fold cross-validation procedure on the whole bank of 16 000 residues occupying a work position.

Bottom Line: From a large set of structural alignments processed from the FSSP database, we selected 1485 structural sub-families including at least 8 members, with accurate alignments and limited redundancy.We show that residues within helices, even when deeply buried, have few non-trivial neighbors (0-2), whereas beta-strand residues clearly exhibit a multimodal behavior, dominated by the local geometry of the tetrahedron (3 non-trivial close neighbors associated with one tetrahedron; 6 with two tetrahedra).Useful topological constraints on the immediate neighborhood of an amino acid, but also on its correlated solvent accessibility, can thus be derived using this approach, from the simple knowledge of multiple sequence alignments.

View Article: PubMed Central - PubMed

Affiliation: Département de Biologie Structurale, Institut de Minéralogie et de Physique des Milieux Condensés, CNRS UMR 7590 - Universités Paris 6/Paris 7, France.

ABSTRACT
Prediction of key features of protein structures, such as secondary structure, solvent accessibility and number of contacts between residues, provides useful structural constraints for comparative modeling, fold recognition, ab-initio fold prediction and detection of remote relationships. In this study, we aim at characterizing the number of non-trivial close neighbors, or long-range contacts of a residue, as a function of its "topohydrophobic" index deduced from multiple sequence alignments and of the secondary structure in which it is embedded. The "topohydrophobic" index is calculated using a two-class distribution of amino acids, based on their mean atom depths. From a large set of structural alignments processed from the FSSP database, we selected 1485 structural sub-families including at least 8 members, with accurate alignments and limited redundancy. We show that residues within helices, even when deeply buried, have few non-trivial neighbors (0-2), whereas beta-strand residues clearly exhibit a multimodal behavior, dominated by the local geometry of the tetrahedron (3 non-trivial close neighbors associated with one tetrahedron; 6 with two tetrahedra). This observed behavior allows the distinction, from sequence profiles, between edge and central beta-strands within beta-sheets. Useful topological constraints on the immediate neighborhood of an amino acid, but also on its correlated solvent accessibility, can thus be derived using this approach, from the simple knowledge of multiple sequence alignments.

No MeSH data available.