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Based on the COMBINE model, together with Brownian dynamics simulations to compute diffusional association rate constants, several mutants were designed to have higher binding affinities than the wild-type proteins.
We argue that the peak scores provide more accurate approximations of the binding affinities than the methods based on transcription factor occupancy [4], [5].
However, binding studies of conformationally constrained peptide analogs of pYEEI show that they have higher binding affinities than the unconstrained pYEEI [10], [11], suggesting that the "two-pronged plug two-holed socket" model may be an oversimplification and that any binding model must take into account the inherent flexibility of short peptides.
As seen in Table 1, these combination linked structures had significantly higher binding affinities than the individual molecules.
The top three TCM compounds, BEMG, ixerisoside, and tangshenoside II, have displayed higher potent binding affinities than the positive control, PNU-142721, in the docking simulation.
Vitro+/vivo- TFBSs indeed have significantly higher intrinsic DNA binding affinities than the other TFBSs (P < 10-, Mann-Whitney U-test; Figure 2).
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Glycosylations of flavones at the 8-C position and isoflavones at the 7-O position show higher binding affinities than those on the other positions of ring A of aglycones.
Moreover, during the Dvl-C peptide titration, a few resonances of the PDZ domain disappeared and reappeared, indicating that the Dvl-C peptide binds to the Dvl1 PDZ domain with higher binding affinity than the Dsh-C peptide does and that the complex is formed in the intermediate exchange range on the NMR time scale.
Docking analysis yielded eight best ligands which have better binding affinity than the standards.
In addition, many tested compounds had higher binding affinity than the AHLs and the furanones that are the inducers and inhibitors of the quorum sensing mechanism, respectively.
This new scaffold exhibited much more potent CXCR4 inhibitory activity, with more than 70% of the compounds showed notably better binding affinity than the reference drug AMD3100 in the binding assay.
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