Commit 270b256f authored by Vladimir Reinharz's avatar Vladimir Reinharz
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Merge branch 'master' of jwgitlab.cs.mcgill.ca:vreinharz/arnhack

parents 1a6e7ba5 ff05270b
......@@ -38,7 +38,7 @@ Dear Dr. Alan Kimmel,
We thank you for giving us an opportunity to improve our manuscript. We do agree with the reviewer that additional validations will improve the impact and significance of our work.\\
We thank the reviewer for pointing at us novel mutate-and-map experiments that have been released after the initial submission of our manuscript. In this revision, we include all new mutate-and-map experiments for which we could (i) identify evolutionary conserved intermolecular interactions, (ii) find an experimentally determined structure in the PDB, and (iii) obtain an alignment from the Rfam family. We provide below a list of all experiments included in our updated benchmark, and a justification for the ones that we could not included inside.
We thank the reviewer for pointing at us novel mutate-and-map experiments that have been released after the initial submission of our manuscript. In this revision, we include all new mutate-and-map experiments for which we could (i) identify evolutionary conserved intermolecular interactions, (ii) find an experimentally determined structure in the PDB, and (iii) obtain an alignment from the Rfam family. We provide below a list of all experiments included in our updated benchmark, and a justification for the ones that we could not included inside.
\section*{Molecules included in the benchmark}
......@@ -91,6 +91,25 @@ The following molecules were not integrated in our benchmark because these are a
\item Tebowned
\end{itemize}
\section*{Detailed answers to the reviewer}
\textbf{Comment:}The authors have not used all the possible experimental data that are available. Just a quick look at a repository https://rmdb.stanford.edu/browse/, I would guess that many of these data sets correspond to structures that have been solved experimentally and for which there are RFAM alignments. These include "add Adenine Riboswitch, V. vulnificus", "16S rRNA Four-Way Junction", "tRNA Phenylalanine, S. cerevisiae", "RNA Puzzle 6" (this is the vitamin B12 riboswitch), and " RNA Puzzle 8" (a SAM riboswitch). These all bind to ligands or proteins, like the 5S RNA and the cyclic di-GMP riboswitch studies in the text, and most of the data sets are associated with publications. It seems that aRNhAck could receive a better test.\\
\textbf{Answer:} \textit{We thank the reviewer to point at the novel experiments posted on the mutate-and-map repository. We do agree that extending the test set will strengthen our manuscript. In this revision, we included all experiments for which we could also find a Rfam alignment and reference structure in the PDB (See above).}\\
\textbf{Comment:} I don't think delta or gamma are defined in the main text (I only figured out what they were by reading the algorithm pseudocode). In fact, there is a statement that delta 'was set to 10'; I think the authors meant lambda.\\
\textbf{Answer:} \textit{This is correct. We added formal definitions of $\delta$ and $\gamma$ in the text, and fixed the typo (Indeed, $\lambda$ is set to 10).}\\
\textbf{Comment:} The main text also skips a step near the end; while it explains which residue *pairs* were considered long-distance functional connections, it does not explain which residues were considered to be interface residues -- both members of the pair?\\
\textbf{Answer:} \textit{We improved the text of the section ``Binding interfaces positions'' to clarify these points.}\\
\textbf{Comment:} In Figure 8, it remains difficult to see the 'bridge' between the red and green parts of the RNA; I suggest putting arrows to mark the two positions, and showing more of the rest of the ribosome, perhaps as white spheres in a cutaway view, to show how the residues are connected via the surrounding complex.\\
\textbf{Answer:} \textit{We updated the Figure as suggested and added arrows to mark the positions. However, we did not managed to produce a clearer picture using a cutaway view.}
\end{document}
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......@@ -424,13 +424,7 @@ The c-di-GMP riboswitch is present in family \texttt{RF01051} in \rfam, which co
{\color{red}
The MaM cobalamin riboswitch sequence can be found in the \rfam family \texttt{RF00174} which has $430$ seed sequences. The PDB contains the structure bounded to its ligand (PDB identifier \texttt{4GXY}). Noticeably, the MaM experiments were done in the presence of cobalamin ligands.
The adenine riboswitch belongs to family \texttt{RF00167} which has $133$ seed sequences. The structure with the adenine ligand�has PDB identifier \texttt {1Y26}. Three different MaM experiments were conducted on this molecule. Experiments \texttt{Adenine\char`_2} and \texttt{Adenine\char`_3} where done in presence of the ligand, and are used in this paper. The third experiment \texttt{Adenine\char`_4} has been performed in absence of the ligand, and thus was omitted from this benchmark since disruptive mutations cannot be used to detect key structural elements of the ligand-bound structure. Nonetheless, the results are indicated in the supplementary material.
}
The adenine riboswitch belongs to family \texttt{RF00167} which has $133$ seed sequences. The structure with the adenine ligand�has PDB identifier \texttt {1Y26}. Three different MaM experiments were conducted on this molecule. Experiments \texttt{Adenine\char`_2} and \texttt{Adenine\char`_3} where done in presence of the ligand, and are used in this paper. The third experiment \texttt{Adenine\char`_4} has been performed in absence of the ligand, and thus was omitted from this benchmark since disruptive mutations cannot be used to detect key structural elements of the ligand-bound structure. Nonetheless, the results are indicated in the supplementary material.}
{\color{red} To complete our benchmark, we also built a secondary test set of \rfam families with experimentally determined 3D structures, but for which MaM experiments were not available.} We selected all \rfam families with sequences having a size ranging from 35 to 150 nucleotides, and with PDB files containing at least one other molecule in the vicinity of the RNA. In total, we found 14 families matching 729 different structures.
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