BackgroundRNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard.ResultsIn this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets.ConclusionsOur method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are real structures, while no deterioration was observed for predicted structures. Design for two structure targets is considerably more difficult, but far from impossible, demonstrating the feasibility of automated design of artificial riboswitches. The Python implementation is available at http://www.stats.ox.ac.uk/research/genome/software/frnakenstein.

Collections of objects such as images are often presented visually in a grid because it is a compact representation that lends itself well for search and exploration. Most grid layouts are sorted using very basic criteria, such as date or filename. In this work we present a method to arrange collections of objects respecting an arbitrary distance measure. Pairwise distances are preserved as much as possible, while still producing the specific target arrangement which may be a 2D grid, the surface of a sphere, a hierarchy, or any other shape. We show that our method can be used for infographics, collection exploration, summarization, data visualization, and even for solving problems such as where to seat family members at a wedding. We present a fast algorithm that can work on large collections and quantitatively evaluate how well distances are preserved.

The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated workflow that allows users to explore the dynamics of a protein binding site and to detect pockets or sub-pockets that may transiently open due to protein internal motion. These transient or cryptic sub-pockets may be of interest in the design and optimization of small molecular inhibitors for a protein target of interest. The TRAPP workflow consists of the following three modules: (i) TRAPP structure— generation of an ensemble of structures using one or more of four possible molecular simulation methods; (ii) TRAPP analysis—superposition and clustering of the binding site conformations either in an ensemble of structures generated in step (i) or in PDB structures or trajectories uploaded by the user; and (iii) TRAPP pocket—detection, analysis, and visualization of the binding pocket dynamics and characteristics, such as volume, solvent-exposed area or properties of surrounding residues. A standard sequence conservation score per residue or a differential score per residue, for comparing on- and off-targets, can be calculated and displayed on the binding pocket for an uploaded multiple sequence alignment file, and known protein sequence annotations can be displayed simultaneously. The TRAPP webserver is freely available at http://trapp.h-its.org.

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Global reconstruction of two-dimensional wall paintings (frescoes) from fragments is an important problem for many archaeological sites. The goal is to find the global position and rotation for each fragment so that all fragments jointly “reconstruct” the original surface (i.e., solve the puzzle). Manual fragment placement is difficult and time-consuming, especially when fragments are irregularly shaped and uncolored. Systems have been proposed to first acquire 3D surface scans of the fragments and then use computer algorithms to solve the reconstruction problem. These systems work well for small test cases and for puzzles with distinctive features, but fail for larger reconstructions of real wall paintings with eroded and missing fragments due to the complexity of the reconstruction search space. We address the search problem with an unsupervised genetic algorithm: we evolve a pool of partial reconstructions that grow through recombination and selection over the course of generations. We introduce a novel algorithm for combining partial reconstructions that is robust to noise and outliers, and we provide a new selection procedure that balances fitness and diversity in the population. In experiments with a benchmark dataset, our algorithm is able to achieve larger and more accurate global reconstructions than previous automatic algorithms.