Simulation of intermediate transport in nanoscale scaffolds for multistep catalytic reactions.

Efficient catalytic cascades that involve several sequential reactions are found frequently in nature. The efficiency of multi-step biochemical pathways is enhanced by substrate channelling, wherein the product of one reaction is directed toward and acts as substrate to the next sequential reaction. Such mechanisms can partially overcome diffusion, which is often fast compared to reaction rates, and promotes loss of intermediates. Biochemical substrate channelling is achieved by the architecture and scaffolding of enzymes, and mimicking these natural structures could lead to innovative catalyst designs. We investigate the efficiency of two channelling approaches - electrostatic interactions and surface adsorption - through continuum modelling, to identify the limits of these modes and the extent to which they can interact. The model considers transport between two active sites where an intermediate is produced at the first active site and consumed at the second. The system includes mass transport through diffusion and migration, and reaction kinetics at the active sites. The effectiveness of this model is quantified by yield of the second reaction relative to the first. Channelling via proximity between active sites and via surface adsorption are found to be inefficient, requiring high values of the rate constant at the second active site to obtain significant yields. The introduction of electrostatic interactions, however, leads to yields of over 90% at much lower values of the rate constant.

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.