3,891 research outputs found
CLP-based protein fragment assembly
The paper investigates a novel approach, based on Constraint Logic
Programming (CLP), to predict the 3D conformation of a protein via fragments
assembly. The fragments are extracted by a preprocessor-also developed for this
work- from a database of known protein structures that clusters and classifies
the fragments according to similarity and frequency. The problem of assembling
fragments into a complete conformation is mapped to a constraint solving
problem and solved using CLP. The constraint-based model uses a medium
discretization degree Ca-side chain centroid protein model that offers
efficiency and a good approximation for space filling. The approach adapts
existing energy models to the protein representation used and applies a large
neighboring search strategy. The results shows the feasibility and efficiency
of the method. The declarative nature of the solution allows to include future
extensions, e.g., different size fragments for better accuracy.Comment: special issue dedicated to ICLP 201
RNAiFold2T: Constraint Programming design of thermo-IRES switches
Motivation: RNA thermometers (RNATs) are cis-regulatory ele- ments that
change secondary structure upon temperature shift. Often involved in the
regulation of heat shock, cold shock and virulence genes, RNATs constitute an
interesting potential resource in synthetic biology, where engineered RNATs
could prove to be useful tools in biosensors and conditional gene regulation.
Results: Solving the 2-temperature inverse folding problem is critical for RNAT
engineering. Here we introduce RNAiFold2T, the first Constraint Programming
(CP) and Large Neighborhood Search (LNS) algorithms to solve this problem.
Benchmarking tests of RNAiFold2T against existent programs (adaptive walk and
genetic algorithm) inverse folding show that our software generates two orders
of magnitude more solutions, thus allow- ing ample exploration of the space of
solutions. Subsequently, solutions can be prioritized by computing various
measures, including probability of target structure in the ensemble, melting
temperature, etc. Using this strategy, we rationally designed two thermosensor
internal ribosome entry site (thermo-IRES) elements, whose normalized
cap-independent transla- tion efficiency is approximately 50% greater at 42?C
than 30?C, when tested in reticulocyte lysates. Translation efficiency is lower
than that of the wild-type IRES element, which on the other hand is fully
resistant to temperature shift-up. This appears to be the first purely
computational design of functional RNA thermoswitches, and certainly the first
purely computational design of functional thermo-IRES elements. Availability:
RNAiFold2T is publicly available as as part of the new re- lease RNAiFold3.0 at
https://github.com/clotelab/RNAiFold and http:
//bioinformatics.bc.edu/clotelab/RNAiFold, which latter has a web server as
well. The software is written in C++ and uses OR-Tools CP search engine.Comment: 24 pages, 5 figures, Intelligent Systems for Molecular Biology (ISMB
2016), to appear in journal Bioinformatics 201
Cost Function Networks to Solve Large Computational Protein Design Problems
International audienc
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