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.

Log D the logarithm (italiclog10) 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.

Log D is one of the important parameters used in Lipinski's rule to assess the druggability of a molecule in pharmaceutical formulations. It stands for the logarithm (log 10 ) of the distribution coefficient (D) of a molecule partitioned between an aqueous phase (buffer solution) and a hydrophobic organic solvent phase (e.g. octanol). By definition, distribution coefficient is the ratio of the concentration of the sum of ionized and unionized species of a molecule distributed between the octanol phase and the aqueous buffer phase. Since the pH affects the ionization of a molecule, Log D value which is dependent on the concentrations of the ionized species also varies with pH. In this work, the conventional algebraic method is compared with a more generalized 'dynamic' approach to model the distribution coefficient of monoprotic, diprotic, monoalkaline, amphoteric, diamino-monoprotic and monoprotic acid in the presence of salt, co-solvent. Recently reported experimental log D data of amphoteric molecules such . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/259770 doi: bioRxiv preprint first posted online Feb. 5, 2018; 2 as Nalidixic acid, Mebendazole, Benazepril and Telmisartan, were analyzed using both these approaches to show their equivalence. GRAPHICAL ABSTRACT

Phase plots of coupled maps have shown turbulent, semi-ordered, intermittent and ordered behaviour as a function of control parameters for networks of uniform scale. We investigate the dependence of coupled map dynamics on scale, i.e. number of neurons. We compare results for globally coupled maps (GCMs) and ones with minor lesions, employing a new chaotic function that we propose. The behaviours are described in terms of phase transformations involving emergence, disappearance, migration, or engulfment of phases.

No abstract