| CPC G16B 15/00 (2019.02) [G06F 30/20 (2020.01); G16B 20/30 (2019.02); G16B 20/50 (2019.02)] | 22 Claims |
|
1. A computer-implemented method, comprising:
(a) generating a residue-based triplet hash data set for each of the residue triplets from a cognate protein binder, the residues known to bind to a target epitope, each cognate protein binder residue comprising a cognate protein binder residue sub-structure comprising sub-structure characteristic atoms, the hash key set constructed using the data on the special position of by nine vertexes corresponding to the positions of nine characteristic atoms of the three residues and nine edges corresponding to the edges from the three triangles
wherein the characteristic atoms of the cognate protein binder residue sub-structure comprise any three of the following: the alpha carbon, the backbone carbon atom derived from the carboxyl group, the backbone nitrogen, the backbone oxygen, and the beta carbon of the side chain;
(b) generating a data set from a 3D database of antibody structures, the dataset comprising triplet hash data on any complementarity-determining region (CDR) residues triplet generated in the same way and the same types of atoms as in step (a);
(c) using the data set obtained in step (b) to computationally select one or more candidate antibody structures from the 3D database of antibody structures by identifying antibody scaffold triplet structures which are able to accommodate the three cognate protein binder residues in the geometrically matched positions in CDRs, by comparing the respective triplet hash key values, each candidate antibody structure comprising 3D spatial data on a first matching residue, a second matching residue and a third matching residue each comprising a matching residue sub-structure comprising 3 matching residue sub-structure characteristic atoms; and
(d) calculating a first set of distances representing separations between all possible pairings between characteristic atoms of the same type in different sub-structures of the cognate protein binder residues;
calculating a second set of distances representing separations between all possible pairings between characteristic atoms of the same type in different sub-structures of the matching residues; and
comparing the first set of distances to the second set of distances, and selecting one or more candidate antibody structures wherein the difference in the distances is within a predetermined separation threshold;
(e) outputting the one or more selected candidate antibody structures in a format suitable for use in a process for manufacturing the one or more selected candidate antibodies; and
(f) manufacturing the one or more selected candidate antibodies using, for each of the selected candidate antibodies, the 3 matching residue sub-structure characteristic atoms of each of the matching residue sub-structures for each of the first matching residue, the second matching residue, and the third matching residue.
|