Synthetic biology is a rapidly emerging discipline with long-term ramifications that range from single-molecule detection within cells to the creation of synthetic genomes and novel life forms. Truly phenomenal results have been obtained by pioneering groups--for instance, combinatorial synthesis genetic networks, genome using BioBricks, hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure target fragment, biomolecular self-assembly pathways, etc. Such...

Intrinsically Disordered Proteins/Regions (IDPs/IDRs) are currently recognized as a widespread phenomenon having key cellular functions. Still, many aspects of the function these proteins need to be unveiled. IDPs conformational flexibility allows them recognize and interact with multiple partners, confers larger interaction surfaces that may increase speed. For this reason, molecular interactions mediated by IDPs/IDRs particularly abundant in certain types protein interactions, such those...

Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields research, poised to radically transform society in 21st century. This paper concerns design ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using we ten cis-cleaving hammerhead ribozymes, are shown be functional by cleavage assay. We...

Hepatitis C virus (HCV) core is a highly conserved and multifunctional protein that forms the viral capsid, making it an attractive target for HCV detection inhibition. Aptamers are in vitro selected, single-stranded nucleic acids (RNA or ssDNA) with growing applicability diagnostics therapy. We have carried out DNA RNA selection against six different variants of protein: two versions full-length genotype 1, hydrophilic domain genotypes 1 to 4. The aptamer populations obtained were analyzed...

Conformational entropy for atomic-level, three dimensional biomolecules is known experimentally to play an important role in protein-ligand discrimination, yet reliable computation of remains a difficult problem. Here we describe the first two accurate and efficient algorithms compute conformational RNA secondary structures, with respect Turner energy model, where free parameters are determined from UV absorption experiments. An algorithm derivational structures had previously been...

Synthetic biology and nanotechnology are poised to make revolutionary contributions the 21st century. In this article, we describe a new web server support in silico RNA molecular design. Given an input target secondary structure, together with optional constraints, such as requiring GC-content lie within certain range, number of strong (GC), weak (AU) wobble (GU) base pairs RNAiFold determines one or more sequences, whose minimum free-energy structure is structure. provides access two...

Several algorithms for RNA inverse folding have been used to design synthetic riboswitches, ribozymes and thermoswitches, whose activity has experimentally validated. The RNAiFold software is unique among approaches in that (exhaustive) constraint programming instead of heuristic methods. For reason, can generate all sequences fold into the target structure or determine there no solution. 2.0 a complete overhaul 1.0, rewritten from now defunct COMET language C++. new code properly extends...

Computational tools are essential in the process of designing a CRISPR/Cas experiment for targeted modification an organism's genome. Among other functionalities, these facilitate design guide-RNA (gRNA) given nuclease that maximizes its binding to intended genomic site, while avoiding undesired sites with similar sequences genome organism interest (off-targets). Due popularity this methodology and rapid pace at which it evolves changes, new computational show up constantly. This turnover,...

Novel tools for in silico design of RNA constructs such as riboregulators are required order to reduce time and cost production the development diagnostic therapeutic advances. Here, we present MoiRNAiFold, a versatile user-friendly tool de novo synthetic design. MoiRNAiFold is based on Constraint Programming it includes novel variable types, heuristics restart strategies Large Neighborhood Search. Moreover, this software can handle dozens constraints quality measures improves features...

Abstract Summary: We have implemented in a single package all the features required for extracting, visualizing and manipulating fully conserved positions as well those with family-dependent conservation pattern multiple sequence alignments. The program allows, among other things, to run different methods extracting these positions, combine results visualize them protein 3D structures spaces. Availability implementation: JDet is multiplatform application written Java. It freely available,...

GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis snRNPs and translation control. Reduced levels confer differential to selective groups mRNAs, biallelic variants reducing stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation can be detrimental as it modifies the steady state mRNAs enhances alternative splicing (AS) events genes broad range cellular processes....

The evolutionary dynamics of molecular populations are strongly dependent on the structure genotype spaces. map between and phenotype determines how easily spaces can be navigated accessibility innovations. In particular, size neutral networks corresponding to specific phenotypes its statistical counterpart, distribution abundance, have been studied through multiple computationally tractable genotype-phenotype maps. this work, we test a theory that predicts abundance asymptotic (given...

Selective translation allows to orchestrate the expression of specific proteins in response different signals through concerted action cis-acting elements and RNA-binding (RBPs). Gemin5 is a ubiquitous RBP involved snRNP assembly. In addition, regulates mRNAs apparently opposite mechanisms action. Here, we investigated differential function by identifying at genome-wide scale associated with polysomes. Among showing Gemin5-dependent enrichment polysomal fractions, identified selective...

RNA inverse folding is the problem of finding one or more sequences that fold into a user-specified target structure s 0, i.e. whose minimum free energy secondary identical to 0. Here we consider ensemble all have low with respect given 0.We introduce program RNAdualPF, which computes dual partition function Z ∗, defined as sum Boltzmann factors exp(-E(a,s 0)/RT) nucleotide compatible Using efficiently sample approximately where additionally user can specify IUPAC sequence constraints at...

The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES are organized in modular domains consisting one or more stem-loops that harbor conserved motifs critical for internal initiation translation. A motif the pyrimidine-tract located upstream functional codon type I and II picornavirus IRES. By computationally designing synthetic RNAs fold into a structure sequesters polypyrimidine tract hairpin, we establish correlation between...

Abstract Motivation: RNA thermometers (RNATs) are cis -regulatory elements 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 synthetic biology, where engineered could prove to be useful tools biosensors conditional gene regulation. Results: Solving 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, first...

Abstract The environmental fate of many functional molecules that are produced on a large scale as precursors or additives to specialty goods (plastics, fibers, construction materials, etc.), let alone those synthesized by the pharmaceutical industry, is generally unknown. Assessing their crucial when taking decisions manufacturing, handling, usage, and release these substances, evaluation toxicity in humans other higher organisms. While this data often hard come by, experimental already...

All possible phenotypes are not equally accessible to evolving populations. In fact, only of large size, i.e. those resulting from many different genotypes, found in populations sequences, presumably because they easier discover and maintain. Genotypes that map these usually form mostly connected genotype networks percolate the space thus guaranteeing access a set alternative phenotypes. Within given environment, where specific phenotypic traits become relevant for adaptation, replicative...

Abstract Background Retroviruses transcribe messenger RNA for the overlapping Gag and Gag-Pol polyproteins, by using a programmed -1 ribosomal frameshift which requires slippery sequence an immediate downstream stem-loop secondary structure, together called stimulating signal (FSS). It follows that molecular evolution of this genomic region HIV-1 is highly constrained, since retroviral genome must contain (sequence constraint), code appropriate peptides in reading frames 0 1 (coding...