Computational analysis of hydrogen bonds in protein–RNA complexes for interaction patterns

Abstract

Structural analysis of protein^RNA complexes is labor-intensive, yet provides insight into the interaction patterns between a protein and RNA. As the number of protein^RNA complex structures reported has increased substantially in the last few years, a systematic method is required for automatically identifying interaction patterns. This paper presents a computational analysis of the hydrogen bonds in the most representative set of protein^RNA complexes. The analysis revealed several interesting interaction patterns. (1) While residues in the L L-sheets favored unpaired nucleotides, residues in the helices showed no preference and residues in turns favored paired nucleotides. (2) The backbone hydrogen bonds were more dominant than the base hydrogen bonds in the paired nucleotides, but the reverse was observed in the unpaired nucleotides. (3) The protein^RNA complexes contained more paired nucleotides than unpaired nucleotides, but the unpaired nucleotides were observed more frequently interacting with the proteins. And (4) Arg^U, Thr^A, Lys^A, and Asn^U were the most frequently observed pairs. The interaction patterns discovered from the analysis will provide us with useful information in predicting the structure of the RNA binding protein and the structure of the protein binding RNA. ß

Prediction of RNA binding sites in proteins from amino acid sequence

“…Arginine-rich motifs (Weiss and Narayana 1998) are abundant in RNA binding sites, and other strong biases in the types of amino acids present in RNA-protein interfaces have been reported in several previous studies (Lustig et al 1997;Jones et al 2001;Kim et al 2003;Jeong et al 2004;Jeong and Miyano 2006). To evaluate whether these primary sequence biases can be effectively exploited in a machine learning approach to identify amino acid sequence correlates of RNA binding sites, we generated a nonredundant data set of 109 RNA binding proteins (see Materials and Methods) to estimate the interface propensity for each amino acid type as follows:…”

“…In contrast, the number of experimentally determined structures for RNA-protein complexes is still relatively small and heavily biased (ribosomal proteins represent z50% of all RNA binding proteins in the Protein Data Bank [PDB]). Nevertheless, several computational analyses of RNA-protein complexes have generated databases of RNA-protein contacts and provided valuable insights into the biophysical basis of interaction patterns between ribonucleotides and amino acids (Cusack 1999;Draper 1999;Jones et al 2001;Kim et al 2003;Hoffman et al 2004;Jeong et al 2004;Jeong and Miyano 2006).…”

Predicting protein-binding RNA nucleotides using the feature-based removal of data redundancy and the interaction propensity of nucleotide triplets

“…To evaluate the effect of different definitions of IP on the prediction performance, we encoded 3 different definitions of IP: the interaction propensity sIP of single nucleotides [7,10], the interaction propensity prev_tIP of nucleotide triplets, which is defined in a similar way as the IP of amino acid triplets used in our previous study [11], and the interaction propensity tIP of nucleotide triplets used in this study. The results shown in Table 3 were obtained by 5-fold cross validation with a window of 15 nucleotides.…”

“…In previous studies, we performed an extensive analysis of the recent structures of protein-RNA complexes and computed several types of interaction propensity (IP) between amino acids and nucleotides [7,10,11]. Our analysis showed that the IP of amino acid triplets had a higher binding specificity than the IP of individual amino acids and that the IP of amino acid triplets was useful for predicting binding sites in proteins [11,12].…”

Mining Molecular Structure Data for the Patterns of Interactions Between Protein and RNA

“…Since our previous study on hydrogen-bonding interactions between protein and RNA (Kim et al, 2003), the structures of many protein-RNA complexes have been determined. In this study we attempt a more rigorous study of the interactions by considering van der Waals interactions as well as hydrogen-bonding interactions in a new, extensive dataset of protein-RNA complexes.…”