From protein structure to an optimized chromatographic capture step using multiscale modeling.

Optimizing a biopharmaceutical chromatographic purification process is currently the greatest challenge during process development. A lack of process understanding calls for extensive experimental efforts in pursuit of an optimal process. In silico techniques, such as mechanistic or data driven modeling, enhance the understanding, allowing more cost-effective and time efficient process optimization.

Experimental characterization and prediction of Escherichia coli host cell proteome retention during preparative chromatography.

Purification of recombinantly produced biopharmaceuticals involves removal of host cell material, such as host cell proteins (HCPs). For lysates of the common expression host Escherichia coli (E. coli) over 1500 unique proteins can be identified.

Proteomics-based method to comprehensively model the removal of host cell protein impurities.

Mechanistic models mostly focus on the target protein and some selected process- or product-related impurities. For a better process understanding, however, it is advantageous to describe also reoccurring host cell protein impurities. Within the purification of biopharmaceuticals, the binding of host cell proteins to a chromatographic resin is far from being described comprehensively.

Predicting protein retention in ion-exchange chromatography using an open source QSPR workflow.

Protein-based biopharmaceuticals require high purity before final formulation to ensure product safety, making process development time consuming. Implementation of computational approaches at the initial stages of process development offers a significant reduction in development efforts. By preselecting process conditions, experimental screening can be limited to only a subset.

Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4.

A wide range of cellular processes requires the formation of multimeric protein complexes. The rise of cryo-electron microscopy (cryo-EM) has enabled the structural characterization of these protein assemblies. The density maps produced can, however, still suffer from limited resolution, impeding the process of resolving structures at atomic resolution.