Abstract
RNA-protein (RNP) interactions play essential roles in many biological processes, such as regulation of co-transcriptional and post-transcriptional gene expression, RNA splicing, transport, storage and stabilization, as well as protein synthesis. An increasing number of RNP structures would aid in a better understanding of these processes. However, due to the technical difficulties associated with experimental determination of macromolecular structures by high-resolution methods, studies on RNP recognition and complex formation present significant challenges. As an alternative, computational prediction of RNP interactions can be carried out. Structural models obtained by theoretical predictive methods are, in general, less reliable compared to models based on experimental measurements but they can be sufficiently accurate to be used as a basis for to formulating functional hypotheses. In this article, we present an overview of computational methods for 3D structure prediction of RNP complexes. We discuss currently available methods for macromolecular docking and for scoring 3D structural models of RNP complexes in particular. Additionally, we also review benchmarks that have been developed to assess the accuracy of these methods.
Highlights
Ribonucleic acid (RNA) plays major roles in various biological processes including protein synthesis and gene regulation at the transcriptional and post-transcriptional level
The protein and RNA can be driven to bind by placing them in appropriate force fields with restraints but in general, MD is incapable of accurately simulating binding events and large conformational changes that occur on time-scales larger than microseconds [94]
The Wang group applied a combination of docking and MD followed by binding energy calculations to identify the binding mode of RNA to carbon storage regulator A protein (CsrA), which was previously unknown [96]
Summary
Ribonucleic acid (RNA) plays major roles in various biological processes including protein synthesis and gene regulation at the transcriptional and post-transcriptional level. RNA-binding domains are typical components of proteins involved in the formation of large RNP complexes such as the ribosome or the spliceosome [22,23] and they occur in proteins that regulate the function of RNAs [24]. Only 2194 macromolecular complexes involving both protein and RNA components (but excluding RNA/DNA hybrids) were available in the PDB Of these structures, 1642 were solved by X-ray crystallography, 426 by EM, 120 by solution NMR spectroscopy and 6 by other methods such as fibre diffraction. This could indicate that many proteins take part in RNP formation as a part of their life cycle; while on the other hand, such large-scale experimental screens may identify proteins that interact with RNA indirectly, for example, as components of larger protein-protein complexes. We focus on RNP docking, scoring functions and on methods for evaluating the accuracy of predictions, in particular, docking benchmarks and affinity datasets
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