1,463 research outputs found
Pathways and kinetic barriers in mechanical unfolding and refolding of RNA and proteins
Using self-organized polymer models, we predict mechanical unfolding and
refolding pathways of ribo-zymes, and the green fluorescent protein. In
agreement with experiments, there are between six and eight unfolding
transitions in the Tetrahymena ribozyme. Depending on the loading rate, the
number of rips in the force-ramp unfolding of the Azoarcus ribozymes is between
two and four. Force-quench refolding of the P4-P6 subdomain of the Tetrahymena
ribozyme occurs through a compact intermediate. Subsequent formation of
tertiary contacts between helices P5b-P6a and P5a/P5c-P4 leads to the native
state. The force-quench refolding pathways agree with ensemble experiments. In
the dominant unfolding route, the N-terminal a helix of GFP unravels first,
followed by disruption of the N terminus b strand. There is a third
intermediate that involves disruption of three other strands. In accord with
experiments, the force-quench refolding pathway of GFP is hierarchic, with the
rate-limiting step being the closure of the barrel.Comment: 33 pages 7 figure
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Polygenic risk scores in imaging genetics: Usefulness and applications
Genetic factors account for up to 80% of the liability for schizophrenia and bipolar disorder. Genome-wide association studies (GWAS) have successfully identified several single nucleotide polymorphisms (SNPs) and genes associated with increased risk for both disorders. Single SNP analyses alone do not address the overall genomic or polygenic architecture of psychiatric disorders as the amount of phenotypic variation explained by each GWAS-supported SNP is small whereas the number of SNPs/regions underlying risk for illness is thought to be very large. The polygenic risk score models the aggregate effect of alleles associated with disease status present in each individual and allows us to utilise the power of large GWAS to be applied robustly in small samples. Here we make the case that risk prediction, intervention and personalised medicine can only benefit with the inclusion of polygenic risk scores in imaging genetics research
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