MOTIVATION: Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. RESULTS: Despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groups of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation. AVAILABILITY AND IMPLEMENTATION: The source code, binaries and data are available at https://simtk.org/home/kgs . CONTACT: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Predicting the three-dimensional structure of a protein from its amino acid sequence is currently one of the most challenging problems in bioinformatics. The internal structure of helices and sheets is highly recurrent and help reduce the search space significantly. However, random coil segments make up nearly 40% of proteins and they do not have any apparent recurrent patterns, which complicates overall prediction accuracy of protein structure prediction methods. Luckily, previous work has indicated that coil segments are in fact not completely random in structure and flanking residues do seem to have a significant influence on the dihedral angles adopted by the individual amino acids in coil segments. In this work we attempt to predict a probability distribution of these dihedral angles based on the flanking residues. While attempts to predict dihedral angles of coil segments have been done previously, none have, to our knowledge, presented comparable results for the probability distribution of dihedral angles. RESULTS: In this paper we develop an artificial neural network that uses an input-window of amino acids to predict a dihedral angle probability distribution for the middle residue in the input-window. The trained neural network shows a significant improvement (4-68%) in predicting the most probable bin (covering a 30 degrees x 30 degrees area of the dihedral angle space) for all amino acids in the data set compared to baseline statistics. An accuracy comparable to that of secondary structure prediction ( approximately 80%) is achieved by observing the 20 bins with highest output values. CONCLUSION: Many different protein structure prediction methods exist and each uses different tools and auxiliary predictions to help determine the native structure. In this work the sequence is used to predict local context dependent dihedral angle propensities in coil-regions. This predicted distribution can potentially improve tertiary structure prediction methods that are based on sampling the backbone dihedral angles of individual amino acids. The predicted distribution may also help predict local structure fragments used in fragment assembly methods.