Local environment effects on charged mutations for developing aggregation-resistant monoclonal antibodies.

ABSTRACT: Protein aggregation is a major concern in biotherapeutic applications of monoclonal antibodies. Introducing charged mutations is among the promising strategies to improve aggregation resistance. However, the impact of such mutations on solubilizing activity depends largely on the inserting location, whose mechanism is still not well understood. Here, we address this issue from a solvation viewpoint, and this is done by analyzing how the change in solvation free energy upon charged mutation is composed of individual contributions from constituent residues. To this end, we perform molecular dynamics simulations for a number of antibody mutants and carry out the residue-wise decomposition of the solvation free energy. We find that, in addition to the previously identified "global" principle e

SUBMITTER: Lee J 

PROVIDER: S-EPMC7713239 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature