Steric Equation of State for Monoclonal Antibodies from Low to High Concentrations

Steric interactions potentially play a significant role in packing behavior of proteins as one considers increasing concentrations, particularly for monoclonal antibodies (MAbs) due to their extended, anisotropic, and flexible structure. Steric contributions to the equation of state are key to balancing attractive contributions in crowded environments that result in phase separation. Steric protein-protein interactions are sensitive to the size and shape of proteins and can be considered as the minimal level of interactions to be captured in coarse-grained models.To date, all atom simulation was used to calculate only the role of steric only behavior of monoclonal antibodies on the second osmotic virial coefficients . A biased Monte Carlo algorithm (Mayer sampling) used to calculate the steric interactions up to the fifth virial coefficient using all atom simulations for representative MAb structures. The results are compared with different levels of coarse grained models to assess the accuracy of predictions of lower resolution models. The results show that, upon increasing concentration to approx. 10 volume percent, the deviation of the predictions of coarse grained models is pronounced, but can be mitigated by the choice of model.