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We performed a second selection of 6 models with binding energies of less than or equal to -11 kcal/mol.
Models with binding to either enzyme state 1 or state 2 are equally able to explain the data.
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The adsorption isotherm for Pb II) fitted well with the Langmuir model, with binding capacities of shell of 28.18 and 8.08 mg/g for NHS and AS, respectively.
The two-compartment model with binding in the central compartment has been developed and analyzed.
The second model was the one-compartment model in equilibrium and the third was the two-compartment model with binding occurring in one compartment (the target site).
A mixed inhibition model with binding corrected by an independent binding model was best able to fit the data (Kic = 19.2 nmol/l and Kin = 39.8 nmol/l) and to predict clinical effect of ketoconazole on midazolam area under the concentration time curve.
Alternative models, with nonproductive binding at states 1, 3, or 4, are not able to explain the observed data nearly as well as the model with inhibition at state 2.
This requirement is not met for all models with inhomogeneous binding.
Despite this, the overall pocket similarity was relatively low (maximum 64%), indicating that PXR is not well conserved in these aquatic vertebrates and that other animal models with higher binding site conservation should also be investigated.
The heat released due to Ca2+ binding to EF2 alone is between the ΔH values for the 1st and 2nd Ca2+ binding, suggesting that the model with independent binding is unlikely.
Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer.
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