RNA tertiary structure prediction using RNAComposer in CASP15

Abstract

As CASP15 participants, in the new category of 3D RNA structure prediction, we applied expert modeling with the support of our proprietary system RNAComposer. Although RNAComposer is primarily known as an automated web server, its features allow it to be used interactively, for example, for homology‐based modeling or assembling models from user‐provided structural elements. In the paper, we present various scenarios of applying the system to predict the 3D RNA structures that we employed. Their combination with expert input, comparative analysis of models, and routines to select representative resultant structures form a ready‐for‐reuse workflow. With selected examples, we demonstrate its application for the in silico modeling of natural and synthetic RNA molecules targeted in CASP15.

Assessment of three‐dimensional RNA structure prediction in CASP15

“…In addition to not using deep learning, the top four RNA predictors shared the property that they were not servers and, based on their own accounts (see papers co-submitted for this CASP issue [65][66][67][68] ), they appeared to still make use of human intuition. While there were cases where server models were more accurate than "human" models from the same laboratory (e.g., Yang), generally server models were worse in quality than the top 4 human predictor groups.…”

“…We note that these top server submissions additionally exhibited secondary structures (Watson-Crick base-pairing) with lower accuracy than some other top predictors, as measured by INF_WC (orange and cyan points, Figure 2), suggesting that there is room for improvement in automated prediction of secondary structure. Furthermore, based on abstracts collected for the CASP15 conference, while the majority of CASP15 RNA predictors groups tested deep learning methods (orange highlights in Figure 4A), the top 4 RNA groups did not use deep learning approaches (see also articles by RNA predictor groups co-submitted for the CASP15 special issue [65][66][67][68] ; and https:// predictioncenter.org/casp15/doc/presentations/Day3/).…”

Stability and affinity evaluation of aptamers as a biorecognition system for testosterone and its analogs

“…Tertiary structures were modeled for each child structure generated using the RNAComposer web server, where the CT format was converted to the dotted bracket format, and on the same server, the tertiary structure was obtained in “.pdb” format (Protein Databank File) [35,36]. Subsequently, the 3DNA-Nucleic Acid Structures web server was used to convert the structures from RNA to DNA [37].…”

“…The RNAComposer is also very often used software in publications that develop tertiary structures, since their in silico approach has proven to be identical to experimentation results, especially for hairpin and small structures. It is based on the automatic translation and a comparative relationship of the secondary structure fragments and the elements of a tertiary structure taking as reference the database "RNA FRABASE", where the structures with the higher negative value of free energy are used for the 3D structure [10,15,35,36].…”

In Vivo and In Vitro Characterization of the RNA Binding Capacity of SETD1A (KMT2F)

“…To gain some insight into the RNA binding capacity of the RRM domain, in addition to R50 (Supplementary Figure S9), we generated 6 further, randomized RNA sequences (50 bp each), picking those that reflected essentially different 3D structures according to RNAcomposer [60,61] outputs. The modeled structures were trimmed (to 30-50 long cores), removing loose, uncoordinated terminal RNA stretches at 3 and 5 ends.…”