A computer-implemented method 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, and wherein the cofactor specificity of the enzyme variant is switched from the first cofactor to the second cofactor, the method comprising at least the steps of: i) 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, ii) providing the amino-acid sequence of the target enzyme, iii) determining an estimated target enzyme-cofactor structure comprising information on a spatial structure of the target enzyme bound to one of the cofactors, iv) 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, wherein for each selected cofactor atom, entries are generated in the interaction matrix that comprise the counts of each amino-acid residue of the target enzyme within a predefined distance to the selected cofactor atom, v) determining a cofactor specificity of the target enzyme by providing 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, wherein the classifier is trained by - providing information on molecular structures of a plurality of enzymes, wherein each molecular structure represents an enzyme bound to the first or the second cofactor, - for each molecular structure, generating the interaction matrix, wherein each interaction matrix is associated to the respective cofactor of the molecular structure, - training the classifier with the interaction matrices so that the classifier is configured to classify the cofactor specificity for the first or the second cofactor of an enzyme based on the entries of the interaction matrix. i) 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, ii) providing the amino-acid sequence of the target enzyme, iii) determining an estimated target enzyme-cofactor structure comprising information on a spatial structure of the target enzyme bound to one of the cofactors, iv) 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, wherein for each selected cofactor atom, entries are generated in the interaction matrix that comprise the counts of each amino-acid residue of the target enzyme within a predefined distance to the selected cofactor atom, v) determining a cofactor specificity of the target enzyme by providing 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, - providing information on molecular structures of a plurality of enzymes, wherein each molecular structure represents an enzyme bound to the first or the second cofactor, - for each molecular structure, generating the interaction matrix, wherein each interaction matrix is associated to the respective cofactor of the molecular structure, - training the classifier with the interaction matrices so that the classifier is configured to classify the cofactor specificity for the first or the second cofactor of an enzyme based on the entries of the interaction matrix.