Journal of Computer-Aided Molecular Design

, Volume 32, Issue 12, pp 1363–1373 | Cite as

Individually double minimum-distance definition of protein–RNA binding residues and application to structure-based prediction

  • Wen Hu
  • Liu Qin
  • Menglong Li
  • Xuemei Pu
  • Yanzhi GuoEmail author


Identifying protein–RNA binding residues is essential for understanding the mechanism of protein–RNA interactions. So far, rigid distance thresholds are commonly used to define protein–RNA binding residues. However, after investigating 182 non-redundant protein–RNA complexes, we find that it would be unsuitable for a certain amount of complexes since the distances between proteins and RNAs vary widely. In this work, a novel definition method was proposed based on a flexible distance cutoff. This method can fully consider the individual differences among complexes by setting a variable tolerance limit of protein–RNA interactions, i.e. the double minimum-distance by which different distance thresholds are achieved for different complexes. In order to validate our method, a comprehensive comparison between our flexible method and traditional rigid methods was implemented in terms of interface structure, amino acid composition, interface area and interaction force, etc. The results indicate that this method is more reasonable because it incorporates the specificity of different complexes by extracting the important residues lost by rigid distance methods and discarding some redundant residues. Finally, to further test our double minimum-distance definition strategy, we developed a classifier to predict those binding sites derived from our new method by using structural features and a random forest machine learning algorithm. The model achieved a satisfactory prediction performance and the accuracy on independent data sets reaches to 85.0%. To the best of our knowledge, it is the first prediction model to define positive and negative samples using a flexible cutoff. So the comparison analysis and modeling results have demonstrated that our method would be a very promising strategy for more precisely defining protein–RNA binding sites.


Protein–RNA interactions Double minimum-distance cutoff RNA-binding residue definition Structural prediction 



This work was funded by the National Natural Science Foundation of China (Nos. 21675114, 21573151).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

10822_2018_177_MOESM1_ESM.doc (296 kb)
Supplementary material 1 (DOC 296 KB)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Wen Hu
    • 1
  • Liu Qin
    • 1
  • Menglong Li
    • 1
  • Xuemei Pu
    • 1
  • Yanzhi Guo
    • 1
    Email author
  1. 1.College of ChemistrySichuan UniversityChengduPeople’s Republic of China

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