ANNaMo: Coarse-grained modeling for folding and assembly of RNA and DNA systems.

The folding of RNA and DNA strands plays crucial roles in biological systems and bionanotechnology. However, studying these processes with high-resolution numerical models is beyond current computational capabilities due to the timescales and system sizes involved. In this article, we present a new coarse-grained model for investigating the folding dynamics of nucleic acids. Our model represents three nucleotides with a patchy particle and is parameterized using well-established nearest-neighbor models. Thanks to the reduction of degrees of freedom and to a bond-swapping mechanism, our model allows for simulations at timescales and length scales that are currently inaccessible to more detailed models. To validate the performance of our model, we conducted extensive simulations of various systems: We examined the thermodynamics of DNA hairpins, capturing their stability and structural transitions, the folding of an MMTV pseudoknot, which is a complex RNA structure involved in viral replication, and also explored the folding of an RNA tile containing a k-type pseudoknot. Finally, we evaluated the performance of the new model in reproducing the melting temperatures of oligomers and the dependence on the toehold length of the displacement rate in toehold-mediated displacement processes, a key reaction used in molecular computing. All in all, the successful reproduction of experimental data and favorable comparisons with existing coarse-grained models validate the effectiveness of the new model.

A Primer on the oxDNA Model of DNA: When to Use it, How to Simulate it and How to Interpret the Results.

The oxDNA model of Deoxyribonucleic acid has been applied widely to systems in biology, biophysics and nanotechnology. It is currently available via two independent open source packages. Here we present a set of clearly documented exemplar simulations that simultaneously provide both an introduction to simulating the model, and a review of the model's fundamental properties. We outline how simulation results can be interpreted in terms of-and feed into our understanding of-less detailed models that operate at larger length scales, and provide guidance on whether simulating a system with oxDNA is worthwhile.

Return probabilities and hitting times of random walks on sparse Erdös-Rényi graphs.

We consider random walks on random graphs, focusing on return probabilities and hitting times for sparse Erdös-Rényi graphs. Using the tree approach, which is expected to be exact in the large graph limit, we show how to solve for the distribution of these quantities and we find that these distributions exhibit a form of self-similarity.

Experimental rabbit model of meningitis produced by Haemophilus influenzae serotype c.

The virulence of Haemophilus influenzae type c when inoculated intracisternally (i.c.) into rabbits was evaluated. Rabbits are relatively resistant to infection with H. influenzae type b, such that inocula of the order of 10(6-9) cfu are required to produce meningitis in this model. In contrast, fatal meningitis was produced in this study when 10(3) cfu of a type-c strain were injected i.c. into rabbits. Numbers of bacteria in cerebrospinal fluid (CSF) of control (untreated) animals generally increased to 10(7) cfu/ml. Increases in white blood cells, protein and lactate in the CSF were similar to those which had been observed during meningitis due to Streptococcus pneumoniae in rabbits. The infection was amenable to therapy with ampicillin 50 mg/kg given intravenously 12 h after infection. Numbers of bacteria in CSF were reduced to 2.2 x 10(3) cfu/ml (SEM 0.2 x 10(3)) at 8 h after treatment with a single dose of ampicillin. Two doses of ampicillin, given 12 and 20 h after infection, significantly increased the mean survival time. In contrast to previous experimental studies with rabbits, the penetration of ampicillin into the CSF was high--46 (SEM 10) % of the blood level. Since considerable replication of H. influenzae type c occurred within the CSF in this model, the nature of the meningeal damage produced was likely to be similar to that which takes place in man. Hence, H. influenzae type c meningitis in rabbits may provide a useful model in which therapeutic and other experimental studies of H. influenzae meningitis can be performed.

Contribution to the problem of cyst-producing coccidians.

The problem of life cycles of cyst-producing coccidians, mainly those of the genus Sarcocystis, from carnivorous birds has been discussed. Oocysts of the "sarcocystic" type have been recovered from 9 species of birds of prey and owls from Czechoslovakia. The course of experimental infection in a group of birds consisting of the species Tyto alba, Asio otus, Strix aluco, Buteo buteo has been described. We inoculated these birds with cystic stages of the genus Sarcocystis obtained from white laboratory mice (Mus musculus) infected previously with oocysts from Tyto alba. The nomenclature of heteroxenous coccidians of the genus Sarcocystis has been discussed and suggestions have been made for the use of simple, one-word specific names. A description is given of a new species of the genus Sarcocystis--Sarcocystis dispersa sp. n. Its asexual development and cyst production in Mus musculus (intermediate host), and cyst production in Tyto alba and Asio otus (definitive hosts) have been studied.