Patent ID: 8762066

Claim:
A method for identifying amino acid residues for variation in a protein variant library in order to affect a desired activity, said method comprising: (a) receiving data characterizing a training set of a protein variant library, wherein the data provides activity and an amino acid sequence for each protein variant in the training set; (b) from the data, developing a sequence-activity model for predicting activity as a function of multiple independent variables, wherein the sequence activity model comprises a plurality of linear terms and one or more non-linear terms, the linear and non-linear terms are separated by plus or minus signs, each linear term comprises the product of a coefficient and a bit-value independent variable, wherein the coefficient of the linear term indicates the relative impact on activity by the bit-value independent variable, and wherein the bit-value independent variable specifies the presence or absence of only one particular amino acid residue of a specific residue type at a specific sequence position, and each non-linear term is a cross-product term comprising the product of a coefficient and two or more bit-value independent variables, wherein the coefficient of the non-linear term indicates the relative impact on activity by the interaction of the two or more bit-value independent variables, and wherein each of the two or more bit-value independent variables specifies the presence or absence of a particular residue of a specific residue type at a specific sequence position; and (c) using the sequence-activity model to identify one or more amino acid residues at specific positions for varying or fixing to impact the desired activity, wherein operations (a)-(c) are performed by executing instructions on a computer system programmed to perform said operations.