Calibrative approaches to protein solubility modeling of a mutant series using physicochemical descriptors

A set of physicochemical properties describing a protein of known structure is employed for a calibrative approach to protein solubility. Common hydrodynamic and electrophoretic properties routinely measured in the bio-analytical laboratory such as zeta potential, dipole moment, the second osmotic virial coefficient are first estimated in silico as a function a pH and solution ionic strength starting with the protein crystal structure. The utility of these descriptors in understanding the solubility of a series of ribonuclease Sa mutants is investigated. A simple two parameter model was trained using solubility data of the wild type protein measured at a restricted number of solution pHs. Solubility estimates of the mutants demonstrate that zeta potential and dipole moment may be used to rationalize solubility trends over a wide pH range. Additionally a calibrative model based on the protein’s second osmotic virial coefficient, B22 was developed. A modified DVLO type potential along with a simplified representation of the protein allowed for efficient computation of the second viral coefficient. The standard error of prediction for both models was on the order of 0.3 log S units. These results are very encouraging and demonstrate that these models may be trained with a small number of samples and employed extrapolatively for estimating mutant solubilities

Pharmaceutical removal during managed aquifer recharge with pretreatment by advanced oxidation

Organic micropollutants (OMPs) are detected in sources for drinking water and treatment possibilities are investigated. Innovative removal technologies are available such as membrane filtration and advanced oxidation, but also biological treatment should be considered. By combining an advanced oxidation process with managed aquifer recharge (MAR), two complementary processes are expected to provide a hybrid system for OMP removal, according to the multiple barrier approach. Laboratory scale batch reactor experiments were conducted to investigate the removal of dissolved organic carbon (DOC) and 14 different pharmaceutically active compounds (PhACs) from MAR influent water and water subjected to oxidation, under different process conditions. A DOC removal of 10% was found in water under oxic (aerobic) conditions for batch reactor experiments, a similar value for DOC removal was observed in the field. Batch reactor experiments for the removal of PhACs showed that the removal of pharmaceuticals ranged from negligible to more than 90%. Under oxic conditions, seven out of 14 pharmaceuticals were removed over 90% and 12 out of 14 pharmaceuticals were removed at more than 50% during 30 days of experiments. Under anoxic conditions, four out of 14 pharmaceuticals were removed over 90% and eight out of 14 pharmaceuticals were removed at more than 50% over 30 days' experiments. Carbamazepine and phenazone were persistent both under oxic and anoxic conditions. The PhACs removal efficiency with oxidized water was, for most compounds, comparable to the removal with MAR influent water