Modeling-Based Monitoring and Control of Protein Crystallization in Bioprocesses

Protein crystallization has evolved from its use for structure determination of biomolecules via X-ray diffraction in the 1960s to industrial applications in the last decades. Generalizing crystallization processes across a wide range of target proteins remains challenging due to narrow and specific windows of viable process parameters. Here, progress on rational methods to monitor and control protein crystallization at multiple scales is presented. While microscopic and macroscopic scales are studied in terms of the phase behavior and process analytical technologies, molecular scales are approached through molecular dynamics simulation and protein engineering.