Beyond rotamers: a generative, probabilistic model of side chains in proteins
<p>Abstract</p> <p>Background</p> <p>Accurately covering the conformational space of amino acid side chains is essential for important applications such as protein design, docking and high resolution structure prediction. Today, the most common way to capture this confo...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
|
| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/11/306 |
| _version_ | 1818664505600638976 |
|---|---|
| author | Frellsen Jes Paluszewski Martin Boomsma Wouter Harder Tim Johansson Kristoffer E Hamelryck Thomas |
| author_facet | Frellsen Jes Paluszewski Martin Boomsma Wouter Harder Tim Johansson Kristoffer E Hamelryck Thomas |
| author_sort | Frellsen Jes |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Accurately covering the conformational space of amino acid side chains is essential for important applications such as protein design, docking and high resolution structure prediction. Today, the most common way to capture this conformational space is through rotamer libraries - discrete collections of side chain conformations derived from experimentally determined protein structures. The discretization can be exploited to efficiently search the conformational space. However, discretizing this naturally continuous space comes at the cost of losing detailed information that is crucial for certain applications. For example, rigorously combining rotamers with physical force fields is associated with numerous problems.</p> <p>Results</p> <p>In this work we present BASILISK: a generative, probabilistic model of the conformational space of side chains that makes it possible to sample in continuous space. In addition, sampling can be conditional upon the protein's detailed backbone conformation, again in continuous space - without involving discretization.</p> <p>Conclusions</p> <p>A careful analysis of the model and a comparison with various rotamer libraries indicates that the model forms an excellent, fully continuous model of side chain conformational space. We also illustrate how the model can be used for rigorous, unbiased sampling with a physical force field, and how it improves side chain prediction when used as a pseudo-energy term. In conclusion, BASILISK is an important step forward on the way to a rigorous probabilistic description of protein structure in continuous space and in atomic detail.</p> |
| first_indexed | 2024-12-17T05:33:49Z |
| format | Article |
| id | doaj.art-7c75cb6bcb9c419f97cf04ddcc83d9c3 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-17T05:33:49Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-7c75cb6bcb9c419f97cf04ddcc83d9c32022-12-21T22:01:40ZengBMCBMC Bioinformatics1471-21052010-06-0111130610.1186/1471-2105-11-306Beyond rotamers: a generative, probabilistic model of side chains in proteinsFrellsen JesPaluszewski MartinBoomsma WouterHarder TimJohansson Kristoffer EHamelryck Thomas<p>Abstract</p> <p>Background</p> <p>Accurately covering the conformational space of amino acid side chains is essential for important applications such as protein design, docking and high resolution structure prediction. Today, the most common way to capture this conformational space is through rotamer libraries - discrete collections of side chain conformations derived from experimentally determined protein structures. The discretization can be exploited to efficiently search the conformational space. However, discretizing this naturally continuous space comes at the cost of losing detailed information that is crucial for certain applications. For example, rigorously combining rotamers with physical force fields is associated with numerous problems.</p> <p>Results</p> <p>In this work we present BASILISK: a generative, probabilistic model of the conformational space of side chains that makes it possible to sample in continuous space. In addition, sampling can be conditional upon the protein's detailed backbone conformation, again in continuous space - without involving discretization.</p> <p>Conclusions</p> <p>A careful analysis of the model and a comparison with various rotamer libraries indicates that the model forms an excellent, fully continuous model of side chain conformational space. We also illustrate how the model can be used for rigorous, unbiased sampling with a physical force field, and how it improves side chain prediction when used as a pseudo-energy term. In conclusion, BASILISK is an important step forward on the way to a rigorous probabilistic description of protein structure in continuous space and in atomic detail.</p>http://www.biomedcentral.com/1471-2105/11/306 |
| spellingShingle | Frellsen Jes Paluszewski Martin Boomsma Wouter Harder Tim Johansson Kristoffer E Hamelryck Thomas Beyond rotamers: a generative, probabilistic model of side chains in proteins BMC Bioinformatics |
| title | Beyond rotamers: a generative, probabilistic model of side chains in proteins |
| title_full | Beyond rotamers: a generative, probabilistic model of side chains in proteins |
| title_fullStr | Beyond rotamers: a generative, probabilistic model of side chains in proteins |
| title_full_unstemmed | Beyond rotamers: a generative, probabilistic model of side chains in proteins |
| title_short | Beyond rotamers: a generative, probabilistic model of side chains in proteins |
| title_sort | beyond rotamers a generative probabilistic model of side chains in proteins |
| url | http://www.biomedcentral.com/1471-2105/11/306 |
| work_keys_str_mv | AT frellsenjes beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins AT paluszewskimartin beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins AT boomsmawouter beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins AT hardertim beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins AT johanssonkristoffere beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins AT hamelryckthomas beyondrotamersagenerativeprobabilisticmodelofsidechainsinproteins |