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

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


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.


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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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Parin Sripakdeevong
    • 1
  • Kyle Beauchamp
    • 1
  • Rhiju Das
    • 1
    • 2
  1. 1.Biophysics ProgramStanford UniversityStanfordUSA
  2. 2.Biochemistry DepartmentStanford UniversityStanfordUSA

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