Recognition of small molecule-RNA binding sites using RNA sequence and structure

Bioinformatics. 2021 Apr 9;37(1):36-42. doi: 10.1093/bioinformatics/btaa1092.

Abstract

Motivation: RNA molecules become attractive small molecule drug targets to treat disease in recent years. Computer-aided drug design can be facilitated by detecting the RNA sites that bind small molecules. However, very limited progress has been reported for the prediction of small molecule-RNA binding sites.

Results: We developed a novel method RNAsite to predict small molecule-RNA binding sites using sequence profile- and structure-based descriptors. RNAsite was shown to be competitive with the state-of-the-art methods on the experimental structures of two independent test sets. When predicted structure models were used, RNAsite outperforms other methods by a large margin. The possibility of improving RNAsite by geometry-based binding pocket detection was investigated. The influence of RNA structure's flexibility and the conformational changes caused by ligand binding on RNAsite were also discussed. RNAsite is anticipated to be a useful tool for the design of RNA-targeting small molecule drugs.

Availability and implementation: http://yanglab.nankai.edu.cn/RNAsite.

Supplementary information: Supplementary data are available at Bioinformatics online.