Computational Study of Coarse-Grained Models for Monoclonal Antibodies

The formulation and delivery of high concentrations of therapeutic biological molecules, such as monoclonal antibodies, is of great interest to the pharmaceutical industry. But the preferred delivery method, subcutaneous injection, cannot be used due to protein aggregation at the concentrations required for the prescribed dosage. In this study, coarse-grained models of monoclonal antibodies at high concentration are developed to provide molecular-level insight into the protein-protein interactions that lead to this phenomenon. The multiscale models are chosen to possess the minimal number of degrees of freedom necessary to capture the generic behavior of a concentrated solution of monoclonal antibodies, and retain the ability to introduce antibody specificity. The thermodynamics and dynamics of the monoclonal antibodies are investigated with grand canonical transition matrix Monte Carlo and molecular dynamics simulations.