Patent ID: 8285666
Filing Date: 2012-10-09
Classification: G16B

Abstract:
1. A method of predicting the individual contribution of a mutated residue or set of mutated residues in a protein to the phenotype conferred by that mutated protein, said method comprising the steps of: (a) generating a 3D model of a complex of a partner molecule bound to said mutated protein by comparison with a 3D model of a complex of the same partner molecule bound to at least one first reference protein; (b) calculating the contribution of the mutated residue to the phenotype conferred by the mutated protein by quantifying the interaction energy between at least two of either (i) the protein and the partner molecule, (ii) the individual protein chains and the partner molecule, (iii) the individual protein residues and the partner molecule, (iv) the protein and the mutated residue, and (v) the individual protein chain(s) and the mutated residue; (c) comparing all or a subset of the contributions calculated in step (b) with the equivalent contribution in the at least one first reference protein complex by carrying out a cascade of dimensionality reduction steps that comprise calculating the Shannon entropy, calculating the Jensen-Shannon divergency, and calculating the information gain; and (d) predicting the phenotype conferred by the mutated protein from the difference in said contributions.