Method and computer program for determining or altering a cofactor specificity of a target enzyme

Abstract

The invention relates to a method and a computer program for determining a cofactor specificity of a target enzyme, wherein the target enzyme is expected to use one of a first cofactor and a second cofactor based on an amino-acid sequence of the target enzyme, and/or for determining an amino-acid sequence of a target enzyme variant, wherein the variant is characterized by a cofactor specificity differing from that of the target enzyme, the method comprising at least the steps of: providing an atomic structure for each of both cofactors, wherein each atomic structure comprises cofactor atoms, and wherein cofactor atoms in the atomic structures that are located at the same corresponding locations in both atomic structures are selected; providing the amino-acid sequence of the target enzyme; determining an estimated target enzyme-cofactor structure comprising information on a spatial structure of the target enzyme bound to one of the cofactors; generating an interaction matrix for the target enzyme-cofactor structure, wherein the interaction matrix comprises entries relating the selected cofactor atoms to surrounding amino-acid residues of the target enzyme; determining a cofactor specificity of the target enzyme by providing the interaction matrix, particularly the entries of the interaction matrix, to a trained classifier that is configured to classify the cofactor specificity of the target enzyme based on the provided interaction matrix to either the first or the second cofactor.

Also published as EP3664095