Pairing a high-resolution statistical potential with a nucleobase-centric sampling algorithm for improving RNA model refinement
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Author(s)
Xiong, P
Wu, R
Zhan, J
Zhou, Y
Year published
2021
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Refining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years’ efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined “native” structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base–base, base–oxygen and oxygen–oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. A total of 4000 quantum-mechanical calculations were performed ...
View more >Refining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years’ efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined “native” structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base–base, base–oxygen and oxygen–oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. A total of 4000 quantum-mechanical calculations were performed to reweight base–base statistical potentials for minimizing possible effects of indirect interactions. The resulting BRiQ knowledge-based potential, equipped with a nucleobase-centric sampling algorithm, provides a robust improvement in refining near-native RNA models generated by a wide variety of modelling techniques.
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View more >Refining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years’ efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined “native” structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base–base, base–oxygen and oxygen–oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. A total of 4000 quantum-mechanical calculations were performed to reweight base–base statistical potentials for minimizing possible effects of indirect interactions. The resulting BRiQ knowledge-based potential, equipped with a nucleobase-centric sampling algorithm, provides a robust improvement in refining near-native RNA models generated by a wide variety of modelling techniques.
View less >
Journal Title
Nature Communications
Volume
12
Issue
1
Copyright Statement
© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Subject
Biostatistics
Clinical sciences
Medical microbiology