Zhu Q(1), Schlick T(1)(2)(3). Author information:
(1)Courant Institute of Mathematical Sciences, New York University, New York,
New York 10012, United States.
(2)Department of Chemistry, New York University, New York, New York 10003,
(3)NYU-ECNU Center for Computational Chemistry, NYU Shanghai, Shanghai 200062,
P. R. China.
Novel RNA motif design is of great practical importance for technology and medicine. Increasingly, computational design plays an important role in such efforts. Our coarse-grained RAG (RNA-As-Graphs) framework offers strategies for enumerating the universe of RNA 2D folds, selecting "RNA-like" candidates for design, and determining sequences that fold onto these candidates. In RAG, RNA secondary structures are represented as tree or dual graphs. Graphs with known RNA structures are called "existing", and the others are labeled "hypothetical". By using simplified features for RNA graphs, we have clustered the hypothetical graphs into "RNA-like" and "non-RNA-like" groups and proposed RNA-like graphs as candidates for design. Here, we propose a new way of designing graph features by using Fiedler vectors. The new features reflect graph shapes better, and they lead to a more clustered organization of existing graphs. We show significant increases in K-means clustering accuracy by using the new features (e.g., up to 95% and 98% accuracy for tree and dual graphs, respectively). In addition, we propose a scoring model for top graph candidate selection. This scoring model allows users to set a threshold for candidates, and it incorporates weighing of existing graphs based on their corresponding number of known RNAs. We include a list of top scored RNA-like candidates, which we hope will stimulate future novel RNA design.
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