Search for: All records

Performing full-resolution atomistic simulations of nucleic acid folding has remained a challenge for biomolecular modeling. Understanding how nucleic acids fold and how they transition between different folded structures as they unfold and refold has important implications for biology. This paper reports a theoretical model and computer simulation of the ab initio folding of DNA inverted repeat sequences. The formulation is based on an all-atom conformational model of the sugar-phosphate backbone via chain closure, and it incorporates three major molecular-level driving forces—base stacking, counterion-induced backbone self-interactions, and base pairing—via separate analytical theories designed to capture and reproduce the effects of the solvent without requiring explicit water and ions in the simulation. To accelerate computational throughput, a mixed numerical/analytical algorithm for the calculation of the backbone conformational volume is incorporated into the Monte Carlo simulation, and special stochastic sampling techniques were employed to achieve the computational efficiency needed to fold nucleic acids from scratch. This paper describes implementation details, benchmark results, and the advantages and technical challenges with this approach.

Homologs of the mutagenic Escherichia coli DNA polymerase V (pol V) are encoded by numerous pathogens and mobile elements. We have used Rum pol (RumA′2B), from the integrative conjugative element (ICE), R391, as a model mobile element-encoded polymerase (MEPol). The highly mutagenic Rum pol is transferred horizontally into a variety of recipient cells, including many pathogens. Moving between species, it is unclear if Rum pol can function on its own or requires activation by host factors. Here, we show that Rum pol biochemical activity requires the formation of a physical mutasomal complex, Rum Mut, containing RumA′2B-RecA-ATP, with RecA being donated by each recipient bacteria. For R391, Rum Mut specific activities in vitro and mutagenesis rates in vivo depend on the phylogenetic distance of host-cell RecA from E. coli RecA. Rum pol is a highly conserved and effective mobile catalyst of rapid evolution, with the potential to generate a broad mutational landscape that could serve to ensure bacterial adaptation in antibiotic-rich environments leading to the establishment of antibiotic resistance.

We investigated the filamentation in air of 7 ps laser pulses of up to 200 mJ energy from a 1.03 μm-wavelength Yb:YAG laser at repetition rates up to$f=1\mathrm{k}\mathrm{H}\mathrm{z}$. Interferograms of the wake generated show that while pulses in a train of repetition rate$f=0.1\mathrm{k}\mathrm{H}\mathrm{z}$encounter a nearly unperturbed environment, at$f=1\mathrm{k}\mathrm{H}\mathrm{z}$, a channel with an axial air density hole of$\sim <\#comment/>20\mathrm{\%<\#comment/>}$is generated and maintained at all times by the cumulative effect of preceding laser pulses. Measurements at$f=1\mathrm{k}\mathrm{H}\mathrm{z}$show that the energy deposited decreases proportional to the air channel density depletion, becoming more pronounced as the repetition rate and pulse energy increase. Numerical simulations indicate that contrary to filaments generated by shorter duration pulses, the electron avalanche is the dominant energy loss mechanism during filamentation with 7 ps pulses. The results are of interest for the atmospheric propagation of joule-level picosecond pulses from Yb:YAG lasers, of which average powers now surpass 1 kW, and for channeling other directed energy beams.