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)...
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doaj-3d9d521691d44c2da215457e4881698a2020-11-24T21:39:00ZengPublic 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 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arvind Ramanathan Andrej J Savol Christopher J Langmead Pratul K Agarwal Chakra S Chennubhotla |
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 |
author_facet |
Arvind Ramanathan Andrej J Savol Christopher J Langmead Pratul K Agarwal Chakra S Chennubhotla |
author_sort |
Arvind Ramanathan |
title |
Discovering conformational sub-states relevant to protein function. |
title_short |
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_sort |
discovering conformational sub-states relevant to protein function. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
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. |
url |
http://europepmc.org/articles/PMC3030567?pdf=render |
work_keys_str_mv |
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