posted on 2024-01-31, 16:36authored byGregory
L. Dignon, Ken A. Dill
Protein–protein
interactions lie at the center of many biological
processes 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 ranks the order of four types of excipients
known to reduce the viscosity of solutions of a particular monoclonal
antibody. This approach appears useful for predicting the effects
of excipients on protein association and phase separation, as well
as the effects of buffers on protein solutions.