Method of thermostabilization of a protein and/or stabilization towards organic solvents

A method of thermo stabilization of a protein and/or stabilization of a protein towards organic solvents wherein the protein contains access routes, comprising

• the following steps:
• a) identification of amino acids forming the bottlenecks of the access routes, wherein said amino acids control the exchange of the solvent between the buried protein core and the surrounding environment and/or in the packing of the amino acids inside the access route;
• b) modification of the amino acids determined in the step a) so that the packing of the amino acids in the bottleneck of the tunnel is improved and the new anatomy of the bottleneck of the access route prevents the access of the undesired solvent molecules to the protein core, while it allows the passage of the molecules necessary for the protein to perform its biological
• function.