18,544 research outputs found
Shapes of interacting RNA complexes
Shapes of interacting RNA complexes are studied using a filtration via their
topological genus. A shape of an RNA complex is obtained by (iteratively)
collapsing stacks and eliminating hairpin loops. This shape-projection
preserves the topological core of the RNA complex and for fixed topological
genus there are only finitely many such shapes.Our main result is a new
bijection that relates the shapes of RNA complexes with shapes of RNA
structures.This allows to compute the shape polynomial of RNA complexes via the
shape polynomial of RNA structures. We furthermore present a linear time
uniform sampling algorithm for shapes of RNA complexes of fixed topological
genus.Comment: 38 pages 24 figure
A tractable genotype-phenotype map for the self-assembly of protein quaternary structure
The mapping between biological genotypes and phenotypes is central to the
study of biological evolution. Here we introduce a rich, intuitive, and
biologically realistic genotype-phenotype (GP) map, that serves as a model of
self-assembling biological structures, such as protein complexes, and remains
computationally and analytically tractable. Our GP map arises naturally from
the self-assembly of polyomino structures on a 2D lattice and exhibits a number
of properties: (genotypes vastly outnumber phenotypes),
(genotypic redundancy varies greatly between
phenotypes), (phenotypes consist
of disconnected mutational networks) and (most
phenotypes can be reached in a small number of mutations). We also show that
the mutational robustness of phenotypes scales very roughly logarithmically
with phenotype redundancy and is positively correlated with phenotypic
evolvability. Although our GP map describes the assembly of disconnected
objects, it shares many properties with other popular GP maps for connected
units, such as models for RNA secondary structure or the HP lattice model for
protein tertiary structure. The remarkable fact that these important properties
similarly emerge from such different models suggests the possibility that
universal features underlie a much wider class of biologically realistic GP
maps.Comment: 12 pages, 6 figure
A creature with a hundred waggly tails: intrinsically disordered proteins in the ribosome
This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. An illustrative example of such disorder-centric functional class is RNA-binding proteins. In this study, we present the results of comprehensive bioinformatics analyses of the abundance and roles of intrinsic disorder in 3,411 ribosomal proteins from 32 species. We show that many ribosomal proteins are intrinsically disordered or hybrid proteins that contain ordered and disordered domains. Predicted globular domains of many ribosomal proteins contain noticeable regions of intrinsic disorder. We also show that disorder in ribosomal proteins has different characteristics compared to other proteins that interact with RNA and DNA including overall abundance, evolutionary conservation, and involvement in protein–protein interactions. Furthermore, intrinsic disorder is not only abundant in the ribosomal proteins, but we demonstrate that it is absolutely necessary for their various functions
Characterization of Aptamer-Protein Complexes by X-ray Crystallography and Alternative Approaches
Aptamers are oligonucleotide ligands, either RNA or ssDNA, selected for high-affinity binding to molecular targets, such as small organic molecules, proteins or whole microorganisms. While reports of new aptamers are numerous, characterization of their specific interaction is often restricted to the affinity of binding (KD). Over the years, crystal structures of aptamer-protein complexes have only scarcely become available. Here we describe some relevant technical issues about the process of crystallizing aptamer-protein complexes and highlight some biochemical details on the molecular basis of selected aptamer-protein interactions. In addition, alternative experimental and computational approaches are discussed to study aptamer-protein interactions.
Size, shape, and flexibility of RNA structures
Determination of sizes and flexibilities of RNA molecules is important in
understanding the nature of packing in folded structures and in elucidating
interactions between RNA and DNA or proteins. Using the coordinates of the
structures of RNA in the Protein Data Bank we find that the size of the folded
RNA structures, measured using the radius of gyration, , follows the Flory
scaling law, namely, \AA where N is the number of
nucleotides. The shape of RNA molecules is characterized by the asphericity
and the shape parameters that are computed using the eigenvalues
of the moment of inertia tensor. From the distribution of , we find
that a large fraction of folded RNA structures are aspherical and the
distribution of values shows that RNA molecules are prolate (). The
flexibility of folded structures is characterized by the persistence length
. By fitting the distance distribution function to the worm-like
chain model we extracted the persistence length . We find that \AA. The dependence of on implies the average length of
helices should increases as the size of RNA grows. We also analyze packing in
the structures of ribosomes (30S, 50S, and 70S) in terms of , ,
, and . The 70S and the 50S subunits are more spherical compared to
most RNA molecules. The globularity in 50S is due to the presence of an
unusually large number (compared to 30S subunit) of small helices that are
stitched together by bulges and loops. Comparison of the shapes of the intact
70S ribosome and the constituent particles suggests that folding of the
individual molecules might occur prior to assembly.Comment: 28 pages, 8 figures, J. Chem. Phys. in pres
Spatial and topological organization of DNA chains induced by gene co-localization
Transcriptional activity has been shown to relate to the organization of
chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In
particular, highly transcribed genes, RNA polymerases and transcription factors
gather into discrete spatial foci called transcription factories. However, the
mechanisms underlying the formation of these foci and the resulting topological
order of the chromosome remain to be elucidated. Here we consider a
thermodynamic framework based on a worm-like chain model of chromosomes where
sparse designated sites along the DNA are able to interact whenever they are
spatially close-by. This is motivated by recurrent evidence that there exists
physical interactions between genes that operate together. Three important
results come out of this simple framework. First, the resulting formation of
transcription foci can be viewed as a micro-phase separation of the interacting
sites from the rest of the DNA. In this respect, a thermodynamic analysis
suggests transcription factors to be appropriate candidates for mediating the
physical interactions between genes. Next, numerical simulations of the polymer
reveal a rich variety of phases that are associated with different topological
orderings, each providing a way to increase the local concentrations of the
interacting sites. Finally, the numerical results show that both
one-dimensional clustering and periodic location of the binding sites along the
DNA, which have been observed in several organisms, make the spatial
co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on
http://dx.doi.org/10.1371/journal.pcbi.100067
Enumeration of chord diagrams on many intervals and their non-orientable analogs
Two types of connected chord diagrams with chord endpoints lying in a
collection of ordered and oriented real segments are considered here: the real
segments may contain additional bivalent vertices in one model but not in the
other. In the former case, we record in a generating function the number of
fatgraph boundary cycles containing a fixed number of bivalent vertices while
in the latter, we instead record the number of boundary cycles of each fixed
length. Second order, non-linear, algebraic partial differential equations are
derived which are satisfied by these generating functions in each case giving
efficient enumerative schemes. Moreover, these generating functions provide
multi-parameter families of solutions to the KP hierarchy. For each model,
there is furthermore a non-orientable analog, and each such model likewise has
its own associated differential equation. The enumerative problems we solve are
interpreted in terms of certain polygon gluings. As specific applications, we
discuss models of several interacting RNA molecules. We also study a matrix
integral which computes numbers of chord diagrams in both orientable and
non-orientable cases in the model with bivalent vertices, and the large-N limit
is computed using techniques of free probability.Comment: 23 pages, 7 figures; revised and extended versio
Aptamer-based therapeutics and their potential in radiopharmaceutical design
Aptamers, short, single stranded oligonucleotide entities, have been developed in the past 15 years against a plethora of targets and for a variety of applications. These range from inhibition of receptors and enzymes to the identification of small molecules in sensor applications, and from the development of targeted therapeutic to the design of novel diagnostic and imaging agents. Furthermore, aptamers have been designed for targets that cover a wide range of diseases, from HIV to tropical diseases, cancer and inflammation. Their easy development and flexibility of use and manipulation, offers further potential. In this paper we review their selection and consider some of the recent applications of aptamers in the design of radiopharmaceuticals for the targeted radiotherapy and medical imaging of disease
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