Zymeworks Inc.

Gregory Lakatos

Surjit Bhimarao Dixit

Anders Ohrn

James Liam McWhirter

Siddharth Srinivasan

Systems, methods and non-transitory computer readable media identify favored polymer conformations. One or more residues are identified and may be replaced in the polymer, or the original primary sequence of the polymer may be retained. The conformations of residues in a subset of residues in a region of the identified one or more residues are altered. This conformational adjustment is repeated for other subsets of residues in the region of the identified one or more residues, and for other conformations, thereby deriving a plurality of polymer structures. A set of clusters is generated for each residue of the polymer using the conformationally adjusted structures, thereby creating sets of clusters. Structures in the plurality of structures are grouped into subgroups when the structures fall into the same clusters across a threshold number of the sets of clusters. One or more physical properties are determined for structures in subgroups, thereby identifying one or more thermodynamically relevant polymer conformations for the polymer.

Systems and methods for identifying thermodynamically relevant polymer conformations

The invention provides a method of determining changes in a first set of residues rdue to changes in a second set of residues rin a protein system comprising one or more proteins comprising rand r. In exemplary embodiments, the method comprises optimizing a quality function Q by modifying one or more properties of rand rin a constrained environment in which all degrees of freedom of the system except those directly involved in the potential coupling between rand rare removed.

Simplifying residue relationships in protein design

Systems and methods for evaluating thermodynamics of atomic changes in a polymer include using a first portion of a refined derived set of three-dimensional coordinates for a derivation of the polymer, which incorporates the atomic change under study, to compute a first effective atomistic Hessian. A second effective atomistic Hessian is computed using a second portion of a refined native set of three-dimensional coordinates for the native polymer. Atoms in the first and second portions are identical. A thermodynamic property of the first portion is determined using the refined derived set of three-dimensional coordinates and the first effective atomistic Hessian. A thermodynamic property of the second portion of the native polymer is determined using the refined native set of three-dimensional coordinates and the second effective atomistic Hessian. The effect of the atomic changes is quantified by taking the difference between the calculated thermodynamic properties of the first and second portions.

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Vancouver, Canada

Gregory Lakatos