A deep learning framework to predict binding preference of RNA constituents on protein surface

Jordy Homing Lam, Yu Li, Lizhe Zhu, Ramzan Umarov, Hanlun Jiang, Amélie Héliou, Fu Kit Sheong, Tianyun Liu, Yongkang Long, Yunfei Li, Liang Fang, Russ B. Altman, Wei Chen, Xuhui Huang, Xin Gao

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Protein-RNA interaction plays important roles in post-transcriptional regulation. However, the task of predicting these interactions given a protein structure is difficult. Here we show that, by leveraging a deep learning model NucleicNet, attributes such as binding preference of RNA backbone constituents and different bases can be predicted from local physicochemical characteristics of protein structure surface. On a diverse set of challenging RNA-binding proteins, including Fem-3-binding-factor 2, Argonaute 2 and Ribonuclease III, NucleicNet can accurately recover interaction modes discovered by structural biology experiments. Furthermore, we show that, without seeing any in vitro or in vivo assay data, NucleicNet can still achieve consistency with experiments, including RNAcompete, Immunoprecipitation Assay, and siRNA Knockdown Benchmark. NucleicNet can thus serve to provide quantitative fitness of RNA sequences for given binding pockets or to predict potential binding pockets and binding RNAs for previously unknown RNA binding proteins.
Original languageEnglish (US)
JournalNature Communications
Issue number1
StatePublished - Oct 30 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): FCC/1/1976-18-01, FCC/1/1976-23-01, FCC/1/1976-25-01, FCC/1/1976-26-01, URF/1/3007-01
Acknowledgements: We are grateful to Wei Wang for helpful discussions. Figure 1 was created by Heno Hwang, scientific illustrator at King Abdullah University of Science and Technology (KAUST). This work was supported by grants from KAUST to X.G. (BAS/1/1624-01, FCC/1/1976-18-01, FCC/1/1976-23-01, FCC/1/1976-25-01, FCC/1/1976-26-01, and FCS/1/4102-02-01) and funding from the KAUST to X.G. and X.H. (URF/1/3007-01). The Hong Kong Research Grant Council (HKUST C6009-15G, AoE/M-09/12, and AoE/P-705/16) and Innovation and Technology Commission (ITCPD/17-9 and ITC-CNERC14SC01) to X.H.; L.F., Y.F.L., and W.C. were supported by Research Grant from Science and Technology Innovation Commission of Shenzhen Municipal Government (No. KQTD20180411143432337 and JCYJ20170307105752508). Part of bioinformatics analysis was supported by the Center for Computational Science and Engineering of Southern University of Science and Technology.


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