US 12,230,363 B2
Efficiently characterizing protein-protein interactions
Ryan Emerson, Seattle, WA (US); Randolph Lopez, Seattle, WA (US); and David Younger, Seattle, WA (US)
Assigned to A-Alpha Bio, Seattle, WA (US)
Filed by A-Alpha Bio, Seattle, WA (US)
Filed on Jul. 5, 2024, as Appl. No. 18/764,600.
Application 18/764,600 is a continuation of application No. PCT/US2023/037104, filed on Nov. 9, 2023.
Claims priority of provisional application 63/424,382, filed on Nov. 10, 2022.
Prior Publication US 2024/0363194 A1, Oct. 31, 2024
Int. Cl. G16B 35/20 (2019.01); C12N 15/10 (2006.01); G16B 15/30 (2019.01)
CPC G16B 15/30 (2019.02) [C12N 15/1037 (2013.01); G16B 35/20 (2019.02)] 18 Claims
 
11. A method of reducing mutation space of a protein-protein interaction (PPI) screening platform, the method comprising:
providing a target library comprising one or more target polypeptide variants of each of two or more different parental target proteins;
measuring binding affinities between each target polypeptide variant of each parental target protein and each of a plurality of binding polypeptides;
clustering, based on the binding affinities, the binding polypeptides using a correlation distance metric and agglomerative hierarchical clustering to identify one or more groups of related binding profiles of the binding polypeptides;
applying a feature selection algorithm to the target library to identify a subset of target polypeptide variants of the one or more target proteins comprising amino acid substitutions that distinguish the one or more groups of related binding profiles from each other for binding to the target protein; and
providing a list of amino acid substitutions that affect PPI, thereby reducing the mutation space of a PPI screening platform.