Periodic Reporting for period 2 - PIPPI (Protein-excipient Interactions and Protein-Protein Interactions in formulation)
Reporting period: 2018-01-01 to 2019-12-31
The consortium were located in Denmark, Sweden, Germany and United Kingdom. The students worked in an international and interdisciplinary network learning to combine systematic investigations of physicochemical behavior of a number of proteins with an in-depth understanding of the molecular interactions behind the macroscopic behavior.
We have published a comprehensive database for diverse protein architectures, which can be interrogated for the prediction of their properties and stability when complemented with a minimum number of experiments. The database contains characterization results from both high throughput methods, structural characterization and in-silico methods. From the 32 articles published so far the synergy between experimental and computational methods and between high-throughput and low-throughput methods are clear.
A systematic study of the overall behaviour of the candidate proteins as a function of pH and ionic strength is almost complete, and will form the basis for further investigations. The protein molecular behaviour has been investigated by structural analyses and the critical formulation attributes have been identified and are being measured over a large space of formulation conditions. Furthermore, the database is online.
The consortium has organised six internal workshops covering formulation development, light scattering, X-ray scattering, nuclear magnetic resonance, molecular dynamics simulations, lyophilization and protein aggregation and data analysis consisting of lectures, exercises and case studies. We organized an international conference on protein stability and aggregation in Heidelberg 2019 https://www.proteininteractions.eu/home/. The ESR students have presented their concepts and results on a large number of international conferences; 32 articles have been published or accepted for publication and at least 30 articles are in preparation.
The massive collaborative efforts in collecting comprehensive data on the same proteins, in the same conditions – stability, modeling, nuclear magnetic resonance, small-angle X-ray scattering, light scattering, rheology to mention some, opens the possibility for unique studies of the interplay between the microscopic atomic structure and the macroscopic overall behavior and stability of the proteins in the library. The data is being deposited in a publicly available database https://pippi-data.kemi.dtu.dk/ which will make it possible for other researchers in the community to benefit from these data in the future. We expect this data will enable us to introduce new tools into the world of biologics for accelerating protein drug development.