Designing optimum protein-excipient interactions using molecular docking simulations

Abstract

As the market for protein drugs is constantly increasing, methods to ensure the stability of the final drug formulation are needed. The choice of excipient in the protein drug formulation can lower the probability of protein aggregation through interactions between the excipient and aggregation prone regions (hot spots) on the protein. The following work uses molecular docking simulations to predict protein excipient interaction regions on the protein and then compares the results with hydrogen- deuterium exchange experiment results. A method using a combination of computer- aided molecular design and molecular docking simulations is proposed to find an optimum excipient minimizing aggregation probability for any particular protein. © 2014 Elsevier B.V.