Toward a Suite of Coarse-Grained Models for Molecular Simulation of Monoclonal Antibodies and Therapeutic Proteins.

A series of coarse-grained models for molecular simulation of proteins are considered, with emphasis on the application of predicting protein-protein self-interactions for monoclonal antibodies (MAbs). As an illustrative example and for quantitative comparison, the models are used to predict osmotic virial coefficients over a broad range of attractive and repulsive self-interactions and solution conditions for a series of MAbs where the second osmotic virial coefficient has been experimentally determined in prior work. The models are compared based on how well they can predict experimental behavior, their computational burdens, and scalability. An intermediate-resolution model is also introduced that can capture specific electrostatic interactions with improved efficiency and similar or improved accuracy when compared to the previously published models. Guidance is included for the selection of coarse-grained models more generally for capturing a balance of electrostatic, steric, and short-ranged nonelectrostatic interactions for proteins from low to high concentrations.