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Defining an Essence of Structure Determining Residue Contacts in Proteins
The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Charac...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778133/ https://www.ncbi.nlm.nih.gov/pubmed/19997489 http://dx.doi.org/10.1371/journal.pcbi.1000584 |
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author | Sathyapriya, R. Duarte, Jose M. Stehr, Henning Filippis, Ioannis Lappe, Michael |
author_facet | Sathyapriya, R. Duarte, Jose M. Stehr, Henning Filippis, Ioannis Lappe, Michael |
author_sort | Sathyapriya, R. |
collection | PubMed |
description | The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Characterisation of this “structural essence” has remained elusive so far: no algorithmic strategy has been devised to-date that could outperform a random selection in terms of 3D reconstruction accuracy (measured as the Ca RMSD). It is not only of theoretical interest (i.e., for design of advanced statistical potentials) to identify the number and nature of essential native contacts—such a subset of spatial constraints is very useful in a number of novel experimental methods (like EPR) which rely heavily on constraint-based protein modelling. To derive accurate three-dimensional models from distance constraints, we implemented a reconstruction pipeline using distance geometry. We selected a test-set of 12 protein structures from the four major SCOP fold classes and performed our reconstruction analysis. As a reference set, series of random subsets (ranging from 10% to 90% of native contacts) are generated for each protein, and the reconstruction accuracy is computed for each subset. We have developed a rational strategy, termed “cone-peeling” that combines sequence features and network descriptors to select minimal subsets that outperform the reference sets. We present, for the first time, a rational strategy to derive a structural essence of residue contacts and provide an estimate of the size of this minimal subset. Our algorithm computes sparse subsets capable of determining the tertiary structure at approximately 4.8 Å Ca RMSD with as little as 8% of the native contacts (Ca-Ca and Cb-Cb). At the same time, a randomly chosen subset of native contacts needs about twice as many contacts to reach the same level of accuracy. This “structural essence” opens new avenues in the fields of structure prediction, empirical potentials and docking. |
format | Text |
id | pubmed-2778133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27781332009-12-08 Defining an Essence of Structure Determining Residue Contacts in Proteins Sathyapriya, R. Duarte, Jose M. Stehr, Henning Filippis, Ioannis Lappe, Michael PLoS Comput Biol Research Article The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Characterisation of this “structural essence” has remained elusive so far: no algorithmic strategy has been devised to-date that could outperform a random selection in terms of 3D reconstruction accuracy (measured as the Ca RMSD). It is not only of theoretical interest (i.e., for design of advanced statistical potentials) to identify the number and nature of essential native contacts—such a subset of spatial constraints is very useful in a number of novel experimental methods (like EPR) which rely heavily on constraint-based protein modelling. To derive accurate three-dimensional models from distance constraints, we implemented a reconstruction pipeline using distance geometry. We selected a test-set of 12 protein structures from the four major SCOP fold classes and performed our reconstruction analysis. As a reference set, series of random subsets (ranging from 10% to 90% of native contacts) are generated for each protein, and the reconstruction accuracy is computed for each subset. We have developed a rational strategy, termed “cone-peeling” that combines sequence features and network descriptors to select minimal subsets that outperform the reference sets. We present, for the first time, a rational strategy to derive a structural essence of residue contacts and provide an estimate of the size of this minimal subset. Our algorithm computes sparse subsets capable of determining the tertiary structure at approximately 4.8 Å Ca RMSD with as little as 8% of the native contacts (Ca-Ca and Cb-Cb). At the same time, a randomly chosen subset of native contacts needs about twice as many contacts to reach the same level of accuracy. This “structural essence” opens new avenues in the fields of structure prediction, empirical potentials and docking. Public Library of Science 2009-12-04 /pmc/articles/PMC2778133/ /pubmed/19997489 http://dx.doi.org/10.1371/journal.pcbi.1000584 Text en Sathyapriya et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sathyapriya, R. Duarte, Jose M. Stehr, Henning Filippis, Ioannis Lappe, Michael Defining an Essence of Structure Determining Residue Contacts in Proteins |
title | Defining an Essence of Structure Determining Residue Contacts in Proteins |
title_full | Defining an Essence of Structure Determining Residue Contacts in Proteins |
title_fullStr | Defining an Essence of Structure Determining Residue Contacts in Proteins |
title_full_unstemmed | Defining an Essence of Structure Determining Residue Contacts in Proteins |
title_short | Defining an Essence of Structure Determining Residue Contacts in Proteins |
title_sort | defining an essence of structure determining residue contacts in proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778133/ https://www.ncbi.nlm.nih.gov/pubmed/19997489 http://dx.doi.org/10.1371/journal.pcbi.1000584 |
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