A method to determine agents for personalized use

A method for identifying one or more compounds specifically binding to a target structure of a given diseased tissue, comprising:

• (i) identifying a mutated gene in the transcriptome of said diseased tissue and identifying at least one mutation comprised in said mutated gene;
• (ii) providing a three-dimensional (3D) structure of a wild-type or homolog protein expressed by a wild-type or homolog gene corresponding to the mutated gene identified in step (i);
• (iii) determining a 3D structure of a mutated protein which is the expression product of the mutated gene identified in step (i) or one or more docking spaces thereof, comprising:
• (a) adapting the amino acid sequence of the 3D structure of the wild-type or homolog protein of step (ii) to the expression product of the mutated gene identified in step (i) and defining one or more docking spaces of the obtained 3D structure of mutated protein, or
• defining one or more docking spaces of the 3D structure of the wild-type or homolog protein of step (ii) and adapting the amino acid sequence of said one or more docking spaces to the expression product of the mutated gene identified in step (i);
• (iv) providing 3D structures of a selection of compounds and fitting each 3D structure of each compound with the one or more docking spaces of step (iii);
• (v) determining the binding affinity of each compound to the one or more docking spaces;
• and
• (vi) identifying one or more compounds specifically binding to the mutated protein.