| Popis: |
As protein drugs become increasing popular therapeutic approaches, formulations must be developed to ensure stability of the final drug product. Lyophilization, or freeze - drying, is an approach commonly used to produce stable protein drugs, yet protein aggregation may still occur in lyophilized formulations. Excipients in the formulation may be selected to reduce the propensity of a protein to aggregate through interaction with aggregation prone regions. In the following work, molecular docking simulations were used to predict the regions on a protein where different excipients were most likely to interact. Simulation results compared variably with experimental hydrogen/deuterium exchange experiments used to determine regions of protein-excipient interactions. The results were used to design formulations for lyophilized calmodulin (PID #1CLL). Sugar and surfactant pairs were selected that would maximize protection of different aggregation prone regions through direct interactions. |
