Modelling of pH-dependence to develop a strategy for stabilising mAbs at acidic steps in production.

ABSTRACT: Engineered proteins are increasingly being required to function or pass through environmental stresses for which the underlying protein has not evolved. A major example in health are antibody therapeutics, where a low pH step is used for purification and viral inactivation. In order to develop a computational model for analysis of pH-stability, predictions are compared with experimental data for the relative pH-sensitivities of antibody domains. The model is then applied to proteases that have evolved to be functional in an acid environment, showing a clear signature for low pH-dependence of stability in the neutral to acidic pH region, largely through reduction of salt-bridges. Interestingly, an extensively acidic protein surface can maintain contribution to structural stabilisation at ac

SUBMITTER: Hebditch M 

PROVIDER: S-EPMC7171260 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature