In Silico Mutagenesis

Building on the structural evaluation and hot spot characterization, Zymeworks’ protein engineers are able to use other components in the ZymeCAD™ platform to extensively model numerous single point and multisite mutations at specific positions of interest.  Apart from remodeling and refining the structure with the altered side chain compositions and coupled backbone conformational changes, extensive scoring techniques are employed to evaluate the stability and other functionally relevant characteristics of the protein. A limited number of the promising protein candidates are expressed and assayed using a variety of in vitro techniques such as chromatography, differential scanning calorimetry, surface plasmon resonance or cell based methods where appropriate. This data is used to drive subsequent iterative optimization cycles of the lead candidates.

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