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Why Can’t We Predict RNA Structure At Atomic Resolution?

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Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 27))

Abstract

No existing algorithm can start with arbitrary RNA sequences and return the precise three-dimensional structures that ensure their biological function. This chapter outlines current algorithms for automated RNA structure prediction (including our own FARNA–FARFAR), highlights their successes, and dissects their limitations, using a tetraloop and the sarcin/ricin motif as examples. The barriers to future advances are considered in light of three particular challenges: improving computational sampling, reducing reliance on experimentally solved structures, and avoiding coarse-grained representations of atomic-level interactions. To help meet these challenges and better understand the current state of the field, we propose an ongoing community-wide CASP-style experiment for evaluating the performance of current structure prediction algorithms.

Sripakdeevong and Beauchamp are equally contributing authors.

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Note added in proof

Since the time of writing (2010), we have described a method called stepwise assembly that appears to resolve the conformational sampling bottleneck for small RNA loops (Sripakdeevong et al. 2011). Further, we and others have initiated RNA-Puzzles, a series of community-wide blind trials for RNA structure prediction (Cruz et al. 2012).

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Correspondence to Rhiju Das .

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Sripakdeevong, P., Beauchamp, K., Das, R. (2012). Why Can’t We Predict RNA Structure At Atomic Resolution?. In: Leontis, N., Westhof, E. (eds) RNA 3D Structure Analysis and Prediction. Nucleic Acids and Molecular Biology, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25740-7_4

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