I Love The Sunshine And Roses

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Conformations of Flanking Bases in HIV-1 RNA DIS Kissing Complexes Studied by Molecular Dynamics

Explicit solvent molecular dynamics simulations (in total almost 800 ns including locally enhanced sampling runs) were applied with different ion conditions and with two force fields (AMBER and CHARMM) to characterize typical geometries adopted by the flanking bases in the RNA kissing-loop complexes. We focus on flanking base positions in multiple x-ray and NMR structures of HIV-1 DIS kissing complexes and kissing complex from the large ribosomal subunit of Haloarcula marismortui. An initial x-ray open conformation of bulged-out bases in HIV-1 DIS complexes, affected by crystal packing, tends to convert to a closed conformation formed by consecutive stretch of four stacked purine bases. This is in agreement with those recent crystals where the packing is essentially avoided. We also observed variants of the closed conformation with three stacked bases, while nonnegligible populations of stacked geometries with bulged-in bases were detected, too. The simulation results reconcile differences in positions of the flanking bases observed in x-ray and NMR studies. Our results suggest that bulged-out geometries are somewhat more preferred, which is in accord with recent experiments showing that they may mediate tertiary contacts in biomolecular assemblies or allow binding of aminoglycoside antibiotics

Computing with bacterial constituents, cells and populations: from bioputing to bactoputing

The relevance of biological materials and processes to computing—aliasbioputing—has been explored for decades. These materials include DNA, RNA and proteins, while the processes include transcription, translation, signal transduction and regulation. Recently, the use of bacteria themselves as living computers has been explored but this use generally falls within the classical paradigm of computing. Computer scientists, however, have a variety of problems to which they seek solutions, while microbiologists are having new insights into the problems bacteria are solving and how they are solving them. Here, we envisage that bacteria might be used for new sorts of computing. These could be based on the capacity of bacteria to grow, move and adapt to a myriad different fickle environments both as individuals and as populations of bacteria plus bacteriophage. New principles might be based on the way that bacteria explore phenotype space via hyperstructure dynamics and the fundamental nature of the cell cycle. This computing might even extend to developing a high level language appropriate to using populations of bacteria and bacteriophage. Here, we offer a speculative tour of what we term bactoputing, namely the use of the natural behaviour of bacteria for calculating

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts