The success in applying therapeutic proteins as drugs over the past twenty years made immunoglobulins one of the most attractive targets for protein engineering. A major challenge in using antibodies as therapeutics is their tendency to form aggregations when stored at high concentrations which is often associated with significant loss in efficacy and increase in immunogenicity. Here, we demonstrate a new method implemented in MOE that identifies aggregation-prone regions in silico. The application calculates hydrophilic and hydrophobic surface patches as well as Accessible Surface Area (ASA), without using very long and computationally expensive molecular dynamics (MD) simulations. A user interface allows for browsing the respective surface patch areas and offers visual support in elucidating or comparing the critical hydrophobic interaction regions within antibodies. This SAR-type approach to protein mutations might help to generate novel protein therapeutics with lower aggregation propensities without compromising target specificity.

New approach for detection and visualization of aggregation-prone regions

253rd National Meeting (2017)

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