Discovering conformational sub-states relevant to protein function.
Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states)...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3030567?pdf=render |
| _version_ | 1817980881127604224 |
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| author | Arvind Ramanathan Andrej J Savol Christopher J Langmead Pratul K Agarwal Chakra S Chennubhotla |
| author_facet | Arvind Ramanathan Andrej J Savol Christopher J Langmead Pratul K Agarwal Chakra S Chennubhotla |
| author_sort | Arvind Ramanathan |
| collection | DOAJ |
| description | Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization.To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function.Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. |
| first_indexed | 2024-04-13T22:58:32Z |
| format | Article |
| id | doaj.art-3d9d521691d44c2da215457e4881698a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T22:58:32Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3d9d521691d44c2da215457e4881698a2022-12-22T02:25:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1582710.1371/journal.pone.0015827Discovering conformational sub-states relevant to protein function.Arvind RamanathanAndrej J SavolChristopher J LangmeadPratul K AgarwalChakra S ChennubhotlaInternal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization.To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function.Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function.http://europepmc.org/articles/PMC3030567?pdf=render |
| spellingShingle | Arvind Ramanathan Andrej J Savol Christopher J Langmead Pratul K Agarwal Chakra S Chennubhotla Discovering conformational sub-states relevant to protein function. PLoS ONE |
| title | Discovering conformational sub-states relevant to protein function. |
| title_full | Discovering conformational sub-states relevant to protein function. |
| title_fullStr | Discovering conformational sub-states relevant to protein function. |
| title_full_unstemmed | Discovering conformational sub-states relevant to protein function. |
| title_short | Discovering conformational sub-states relevant to protein function. |
| title_sort | discovering conformational sub states relevant to protein function |
| url | http://europepmc.org/articles/PMC3030567?pdf=render |
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