Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains un...

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Vydáno v:PLoS computational biology Ročník 15; číslo 2; s. e1006801
Hlavní autoři: Zhou, Hongyu, Dong, Zheng, Verkhivker, Gennady, Zoltowski, Brian D., Tao, Peng
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 01.02.2019
Public Library of Science (PLoS)
Témata:
Algorithms
Allosteric properties
Allosteric proteins
Artificial intelligence
Biology and Life Sciences
Chemical bonds
Circadian rhythm
Circadian rhythms
Classification
Computer and Information Sciences
Computer applications
Covalent bonds
Gene expression
Investigations
Learning algorithms
Light
Linear algebra
Machine learning
Markov chains
Mathematical models
Neural networks
Novels
Observations
Photosensitivity
Physical Sciences
Physiological aspects
Protein binding
Proteins
Quantitative analysis
Research and Analysis Methods
United States > US
Texas
California
ISSN:1553-7358, 1553-734X, 1553-7358
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Popis
Shrnutí:The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an atomistic allosteric mechanism leading to the discovery of the unexpected importance of A'α/Aβ and previously overlooked Eα/Fα loops in the conformational change. This approach could be applicable to other allosteric proteins in general to provide interpretable atomistic representations of their otherwise elusive allosteric mechanisms.
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The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1006801