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A Search for Energy Minimized Sequences of Proteins
In this paper, we present numerical evidence that supports the notion of minimization in the sequence space of proteins for a target conformation. We use the conformations of the real proteins in the Protein Data Bank (PDB) and present computationally efficient methods to identify the sequences with...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724685/ https://www.ncbi.nlm.nih.gov/pubmed/19690619 http://dx.doi.org/10.1371/journal.pone.0006684 |
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author | Jha, Anupam Nath Ananthasuresh, G. K. Vishveshwara, Saraswathi |
author_facet | Jha, Anupam Nath Ananthasuresh, G. K. Vishveshwara, Saraswathi |
author_sort | Jha, Anupam Nath |
collection | PubMed |
description | In this paper, we present numerical evidence that supports the notion of minimization in the sequence space of proteins for a target conformation. We use the conformations of the real proteins in the Protein Data Bank (PDB) and present computationally efficient methods to identify the sequences with minimum energy. We use edge-weighted connectivity graph for ranking the residue sites with reduced amino acid alphabet and then use continuous optimization to obtain the energy-minimizing sequences. Our methods enable the computation of a lower bound as well as a tight upper bound for the energy of a given conformation. We validate our results by using three different inter-residue energy matrices for five proteins from protein data bank (PDB), and by comparing our energy-minimizing sequences with 80 million diverse sequences that are generated based on different considerations in each case. When we submitted some of our chosen energy-minimizing sequences to Basic Local Alignment Search Tool (BLAST), we obtained some sequences from non-redundant protein sequence database that are similar to ours with an E-value of the order of 10(-7). In summary, we conclude that proteins show a trend towards minimizing energy in the sequence space but do not seem to adopt the global energy-minimizing sequence. The reason for this could be either that the existing energy matrices are not able to accurately represent the inter-residue interactions in the context of the protein environment or that Nature does not push the optimization in the sequence space, once it is able to perform the function. |
format | Text |
id | pubmed-2724685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27246852009-08-19 A Search for Energy Minimized Sequences of Proteins Jha, Anupam Nath Ananthasuresh, G. K. Vishveshwara, Saraswathi PLoS One Research Article In this paper, we present numerical evidence that supports the notion of minimization in the sequence space of proteins for a target conformation. We use the conformations of the real proteins in the Protein Data Bank (PDB) and present computationally efficient methods to identify the sequences with minimum energy. We use edge-weighted connectivity graph for ranking the residue sites with reduced amino acid alphabet and then use continuous optimization to obtain the energy-minimizing sequences. Our methods enable the computation of a lower bound as well as a tight upper bound for the energy of a given conformation. We validate our results by using three different inter-residue energy matrices for five proteins from protein data bank (PDB), and by comparing our energy-minimizing sequences with 80 million diverse sequences that are generated based on different considerations in each case. When we submitted some of our chosen energy-minimizing sequences to Basic Local Alignment Search Tool (BLAST), we obtained some sequences from non-redundant protein sequence database that are similar to ours with an E-value of the order of 10(-7). In summary, we conclude that proteins show a trend towards minimizing energy in the sequence space but do not seem to adopt the global energy-minimizing sequence. The reason for this could be either that the existing energy matrices are not able to accurately represent the inter-residue interactions in the context of the protein environment or that Nature does not push the optimization in the sequence space, once it is able to perform the function. Public Library of Science 2009-08-19 /pmc/articles/PMC2724685/ /pubmed/19690619 http://dx.doi.org/10.1371/journal.pone.0006684 Text en Jha 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 Jha, Anupam Nath Ananthasuresh, G. K. Vishveshwara, Saraswathi A Search for Energy Minimized Sequences of Proteins |
title | A Search for Energy Minimized Sequences of Proteins |
title_full | A Search for Energy Minimized Sequences of Proteins |
title_fullStr | A Search for Energy Minimized Sequences of Proteins |
title_full_unstemmed | A Search for Energy Minimized Sequences of Proteins |
title_short | A Search for Energy Minimized Sequences of Proteins |
title_sort | search for energy minimized sequences of proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724685/ https://www.ncbi.nlm.nih.gov/pubmed/19690619 http://dx.doi.org/10.1371/journal.pone.0006684 |
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