A method of computational chemistry for calculating binding free energy/ies of a molecule binding to a macromolecular receptor using data derived from classical simulations, which are carried out in a mixed explicit solvent, comprising: a) inputting the 3D structure of a macromolecular receptor in a computer system; b) building at least one co-solvated simulation system comprising the macromolecular receptor and a mixture of explicit solvents comprising water and at least one organic amphiphilic co-solvent; c) assigning atom types to the atoms in the solvent molecules of the at least one co-solvated simulation system of step b); d) calculating at least one trajectory of the at least one co-solvated simulation system; e) partitioning the at least one co-solvated simulation system into volume elements; f) counting the presence of each solvent atom type in each volume element along the at least one trajectory of the at least one co-solvated simulation system to give the total occupancy over the simulated time in the volume element; g) using the results in the last step for obtaining free energies of binding to the macromolecule of the different atom types found in the solvent molecules; h) decoupling the contribution of each atom type in the co-solvent molecule from the rest of atom types of the co-solvent molecule to obtain corrected free energies of binding of the atom type in each volume element by carrying out a step selected from the group consisting of: h1) in step f) redistributing the count units amongst the atom types of the co-solvent molecule so that the count assigned to the atom type is directly proportional to its binding free energy contribution; and h2) in step g) subtracting the binding free energy due to all the other atom types present in the co-solvent molecule from the uncorrected binding free energy of the atom type. i) gathering all the corrected free energies of binding obtained in step h) for all the atom types to build a corrected scoring function; and j) based on docking, calculating the binding free energy of the molecule binding to the macromolecular receptor using the corrected scoring function obtained in step i). a) inputting the 3D structure of a macromolecular receptor in a computer system; b) building at least one co-solvated simulation system comprising the macromolecular receptor and a mixture of explicit solvents comprising water and at least one organic amphiphilic co-solvent; c) assigning atom types to the atoms in the solvent molecules of the at least one co-solvated simulation system of step b); d) calculating at least one trajectory of the at least one co-solvated simulation system; e) partitioning the at least one co-solvated simulation system into volume elements; f) counting the presence of each solvent atom type in each volume element along the at least one trajectory of the at least one co-solvated simulation system to give the total occupancy over the simulated time in the volume element; g) using the results in the last step for obtaining free energies of binding to the macromolecule of the different atom types found in the solvent molecules; h) decoupling the contribution of each atom type in the co-solvent molecule from the rest of atom types of the co-solvent molecule to obtain corrected free energies of binding of the atom type in each volume element by carrying out a step selected from the group consisting of: h1) in step f) redistributing the count units amongst the atom types of the co-solvent molecule so that the count assigned to the atom type is directly proportional to its binding free energy contribution; and h2) in step g) subtracting the binding free energy due to all the other atom types present in the co-solvent molecule from the uncorrected binding free energy of the atom type. h1) in step f) redistributing the count units amongst the atom types of the co-solvent molecule so that the count assigned to the atom type is directly proportional to its binding free energy contribution; and h2) in step g) subtracting the binding free energy due to all the other atom types present in the co-solvent molecule from the uncorrected binding free energy of the atom type. i) gathering all the corrected free energies of binding obtained in step h) for all the atom types to build a corrected scoring function; and j) based on docking, calculating the binding free energy of the molecule binding to the macromolecular receptor using the corrected scoring function obtained in step i).