A computational procedure for predicting excipient effects on protein-protein affinities.

ABSTRACT: Protein-protein interactions lie at the center of much biology and are a challenge in formulating biological drugs such as antibodies. A key to mitigating protein association is to use small molecule additives, i.e. excipients that can weaken protein-protein interactions. Here, we develop a computationally efficient model for predicting the viscosity-reducing effect of different excipient molecules by combining atomic-resolution MD simulations, binding polynomials and a thermodynamic perturbation theory. In a proof of principle, this method successfully rank orders four types of excipients known to reduce the viscosity of solutions of a particular monoclonal antibody. This approach appears useful for predicting effects of excipients on protein association and phase separation, as well as t

SUBMITTER: Dignon GL 

PROVIDER: S-EPMC10769426 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature