Alkan Kabakcioglu

Twist-writhe partitioning in a coarse-grained DNA minicircle model.

Here we present a systematic study of supercoil formation in DNA minicircles under varying linking number by using molecular-dynamics simulations of a two-bead coarse-grained model. Our model is designed with the purpose of simulating long chains without sacrificing the characteristic structural properties of the DNA molecule, such as its helicity, backbone directionality, and the presence of major and minor grooves. The model parameters are extracted directly from full-atomistic simulations of DNA oligomers via Boltzmann inversion; therefore, our results can be interpreted as an extrapolation of those simulations to presently inaccessible chain lengths and simulation times. Using this model, we measure the twist/writhe partitioning in DNA minicircles, in particular its dependence on the chain length and excess linking number. We observe an asymmetric supercoiling transition consistent with experiments. Our results suggest that the fraction of the linking number absorbed as twist and writhe is nontrivially dependent on chain length and excess linking number. Beyond the supercoiling transition, chains of the order of one persistence length carry equal amounts of twist and writhe. For longer chains, an increasing fraction of the linking number is absorbed by the writhe.

The Information Coded in the Yeast Response Elements Accounts for Most of the Topological Properties of Its Transcriptional Regulation Network.

The regulation of gene expression in a cell relies to a major extent on transcription factors, proteins which recognize and bind the DNA at specific binding sites (response elements) within promoter regions associated with each gene. We present an information theoretic approach to modeling transcriptional regulatory networks, in terms of a simple “sequence-matching” rule and the statistics of the occurrence of binding sequences of given specificity in random promoter regions. The crucial biological input is the distribution of the amount of information coded in these cognate response elements and the length distribution of the promoter regions. We provide an analysis of the transcriptional regulatory network of yeast Saccharomyces cerevisiae, which we extract from the available databases, with respect to the degree distributions, clustering coefficient, degree correlations, rich-club coefficient and the k-core structure. We find that these topological features are in remarkable agreement with those predicted by our model, on the basis of the amount of information coded in the interaction between the transcription factors and response elements.

Statistical properties of contact vectors.

We study the statistical properties of contact vectors, a construct to characterize a proteins structure. The contact vector of an N-residue protein is a list of N integers n(i), representing the number of residues in contact with residue i. We study analytically (at mean-field level) and numerically the amount of structural information contained in a contact vector. Analytical calculations reveal that a large variance in the contact numbers reduces the degeneracy of the mapping between contact vectors and structures. Exact enumeration for lengths up to N=16 on the three-dimensional cubic lattice indicates that the growth rate of number of contact vectors as a function of N is only 3% less than that for contact maps. In particular, for compact structures we present numerical evidence that, practically, each contact vector corresponds to only a handful of structures. We discuss how this information can be used for better structure prediction.

Scale-free network on Euclidean space optimized by rewiring of links

A Barabasi–Albert scale-free network is constructed whose nodes are the Poisson distributed random points within a unit square and links are the straight line connections among the nodes. The cost function, which is the total wiring length associated with such a network defined on a two-dimensional plane, is optimized. The optimization process consists of random selection of a pair of links and rewiring them to reduce the total length of the pair but with the constraint that the degree as well as the out-degree and in-degree of each node are precisely maintained. The resulting optimized network has a small diameter as well as high clustering and the link-length distribution has a stretched exponential tail.

Scale-free network hidden in a collapsing polymer.

We show that the collapsed globular phase of a polymer accommodates a scale-free incompatibility graph of its contacts. The degree distribution of this network is found to decay with the exponent gamma=1/(2-c) up to a cutoff degree dc proportional to L(2-c), where is the loop exponent for dense polymers (c=11/8 in two dimensions) and is the length of the polymer. Our results exemplify how a scale-free network can emerge from standard criticality.

Genome-wide target analysis of NEUROD2 provides new insights into regulation of cortical projection neuron migration and differentiation

BackgroundCellular differentiation programs are controlled, to a large extent, by the combinatorial functioning of specific transcription factors. Cortical projection neurons constitute the major excitatory neuron population within the cortex and mediate long distance communication between the cortex and other brain regions. Our understanding of effector transcription factors and their downstream transcriptional programs that direct the differentiation process of cortical projection neurons is far from complete.ResultsIn this study, we carried out a ChIP-Seq (chromatin-immunoprecipitation and sequencing) analysis of NEUROD2, an effector transcription factor expressed in lineages of cortical projection neurons during the peak of cortical excitatory neurogenesis. Our results suggest that during cortical development NEUROD2 targets key genes that are required for Reelin signaling, a major pathway that regulates the migration of neurons from germinal zones to their final layers of residence within the cortex. We also find that NEUROD2 binds to a large set of genes with functions in layer-specific differentiation and in axonal pathfinding of cortical projection neurons.ConclusionsOur analysis of in vivo NEUROD2 target genes offers mechanistic insight into signaling pathways that regulate neuronal migration and axon guidance and identifies genes that are likely to be required for proper cortical development.

Pseudoknots in a homopolymer

After a discussion of the definition and number of pseudoknots, we reconsider the self-attracting homopolymer paying particular attention to the scaling of the pseudoknot number (Npk) at different temperature regimes in two and three dimensions. We find that, although the total number of pseudoknots is extensive at all temperatures, the number of those forming between the two halves of the chain diverges logarithmically at (both dimensions) and below (two dimensions only) the theta temperature. We later introduce a simple model that emphasizes the role of pseudoknot formation during collapse. The resulting phase diagram involves swollen, branched, and collapsed homopolymer phases with transitions between each pair.

Anharmonicity, mode-coupling and entropy in a fluctuating native protein

We develop a general framework for the analysis of residue fluctuations that simultaneously incorporates anharmonicity and mode-coupling in a unified formalism. We show that both deviations from the Gaussian model are important for modeling the multidimensional energy landscape of the protein Crambin (1EJG) in the vicinity of its native state. The effect of anharmonicity and mode-coupling on the fluctuational entropy is in the order of a few percent.

Macroscopic loop formation in circular DNA denaturation.

The statistical mechanics of DNA denaturation under fixed linking number is qualitatively different from that of unconstrained DNA. Quantitatively different melting scenarios are reached from two alternative assumptions, namely, that the denatured loops are formed at the expense of (i) overtwist or (ii) supercoils. Recent work has shown that the supercoiling mechanism results in a picture similar to Bose-Einstein condensation where a macroscopic loop appears at T{c} and grows steadily with temperature, while the nature of the denatured phase for the overtwisting case has not been studied. By extending an earlier result, we show here that a macroscopic loop appears in the overtwisting scenario as well. We calculate its size as a function of temperature and show that the fraction of the total sum of microscopic loops decreases above T{c}, with a cusp at the critical point.

Denaturation of circular DNA: supercoils and overtwist.

The denaturation transition of circular DNA is studied within a Poland-Scheraga-type approach, generalized to account for the fact that the total linking number (LK), which measures the number of windings of one strand around the other, is conserved. In the model the LK conservation is maintained by invoking both overtwisting and writhing (supercoiling) mechanisms. This generalizes previous studies, which considered each mechanism separately. The phase diagram of the model is analyzed as a function of the temperature and the elastic constant κ associated with the overtwisting energy for any given loop entropy exponent c. As in the case where the two mechanisms apply separately, the model exhibits no denaturation transition for c ≤ 2. For c > 2 and κ = 0 we find that the model exhibits a first-order transition. The transition becomes of higher order for any κ > 0. We also calculate the contribution of the two mechanisms separately in maintaining the conservation of the linking number and find that it is weakly dependent on the loop exponent c.