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Biophysical techniques such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) are routinely used to ascertain the global binding mechanisms of protein-protein or protein-ligand interaction. Recently, Dumas etal, have explicitly modelled the instrument response of the ligand dilution and analysed the ITC thermogram to obtain kinetic rate constants. Adopting a similar approach, we have integrated the dynamic instrument response with the binding mechanism to simulate the ITC profiles of equivalent and independent binding sites, equivalent and sequential binding sites and aggregating systems. The results were benchmarked against the standard commercial software Origin-ITC. Further, the experimental ITC chromatograms of 2'-CMP + RNASE and BH3I-1 + hBCLXL interactions were analysed and shown to be comparable with that of the conventional analysis. Dynamic approach was applied to simulate the SPR profiles of a two-state model, and could reproduce the experimental profile accurately.
RESUMO
[This corrects the article DOI: 10.1016/j.bbrep.2019.100712.].
RESUMO
[This corrects the article DOI: 10.1016/j.bbrep.2019.100712.].
RESUMO
Log D the logarithm ( log10 ) of the distribution coefficient ( D ), is one of the important parameters used in Lipinski's rule to assess the druggability of a molecule in pharmaceutical formulations. The distribution of a molecule between a hydrophobic organic phase and an aqueous buffer phase is influenced by the pH of the buffer system. In this work, we used both the conventional algebraic method and the generalized 'dynamic' approach to model the distribution coefficient of amphoteric, diamino-monoprotic molecule and monoprotic acid in the presence of salt or co-solvent. We have shown the equivalence of these methods by analysing the recently reported experimental data of amphoteric molecules such as nalidixic acid, mebendazole, benazepril and telmisartan.