From Colloidal Self Interactions to Self-Association of Therapeutic Proteins w/ Christopher Roberts

8 May, 2024
This webinar is part of the Antibodies in Solution webinar series at LINXS.
Title: From Colloidal Self Interactions to Self-Association of Therapeutic Proteins: Combining Experimental & Computational Tools
Speaker: Christopher Roberts, University of Delaware, USA
Abstract:
Protein-protein self-interactions are involved in a number of important aspects of controlling the solution properties and stability of therapeutic proteins that affect how challenging it can be to develop a viable drug product for biotherapeutics such as monoclonal antibodies (MAbs) and novel engineered antibody formats with antibodies or antibody fragments with payload proteins / domains (e.g., Fc-fusion constructs). This presentation focuses on a combination of experimental approaches to characterize protein-protein interactions such as small-angle static and dynamic scattering methods, along with coarse-grained molecular models to help address issues such as: predicting high-concentration behaviour; identifying which domains or regions of a protein are most promising to “redevelop” to improve net protein-protein interactions and solution behaviour; and identifying key amino acids for targeted “local protein engineering” to improve the drug product physical characteristics while minimizing risk to clinical efficacy. Examples include a series of MAbs at low and high concentration conditions and a set of Fc-fusion protein constructs (monovalent and bivalent). The results highlight that coarse-grained models with sufficient granularity at the level of charge distributions can offer a useful computationally accessible balance for predicting key experimental behaviour with computational burden that should be reasonable for scaling to the larger needs of the industry.