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. 2023 Feb 23;15(1):2171248. doi: 10.1080/19420862.2023.2171248

Figure 2.

On the left, a funnel showing various knowledge-based approaches and used to predict the developability properties of biologics. To the right, antibodies with different folding and hydrophobicity illustrate examples of physics-based properties important for the developability. Sequence and structure-based approaches to characterize the biophysical properties of antibodies. On the left, a funnel is depicted containing circles highlighting the critical steps in predicting biophysical properties from sequences (in the background), such as big data, neuronal networks, and multiple sequence alignments. On the right, the physics-based approaches are represented by a schematic representation of the different conformational states an antibody can adopt, such as the partially unfolded (red), the non-binding (green) and the binding competent state (blue) A). B) The unfolded antibodies (red) are shown as aggregates. C) and D) show antibody surfaces of the same antibody colored by their surface hydrophobicity. The areas of high surface hydrophobicity differ with different conformations.

Knowledge and physics-based approaches for characterizing biophysical properties of antibodies. Left panel, knowledge-based: Overview of critical steps for sequence-based in silico prediction of biophysical properties from several thousands of potential hit sequences. Right panel, physics-based: A) The antibody binding interface exists as an ensemble of conformations, which includes binding competent as well as non-binding states. Partially unfolded conformations also exist with a lower probability. B) Different conformations exhibit different properties, where partially unfolded conformations may aggregate which leads to further unfolding. In C) and D), the hydrophobicity profile of two different conformations of the TNF-α binding antibody golimumab is mapped on its molecular surface using localized free energy of hydration. The two conformations show a significantly altered hydrophobicity profile and will therefore most likely interact differently with other hydrophobic molecules.