Background Pim1 is a unique protein kinase because it has a proline residue located in the hinge region which precludes the canonical second hydrogen bond between the hinge backbone and the adenine moiety of ATP. Mutants of Pim1 have been crystallized to see if mutating the proline residue can restore the ATP binding pocketed to that of a typical kinase. As an example we will make a P123M mutation of PIM1.

• Type pdb code 1yxu into the PDB search tab.
• Convert the PDB file into an ICM object.
• Select residue number 123 in the "a" subunit
• Right click on the selection in the graphical workspace or ICM workspace and select Advanced/Mutate Amino-Acid
• Select Methionine from the drop down list.

• Now optimize the side chains surrounding the residue.
• Right click on Methionine 123 and select Neigbors/5A > Same Object >include source
• Right click on the selection and choose Advanced/Optimize Side Chains
• The higher the number of calls per variable the longer the simulation. The default number has been shown to provide an ideal simulation length. Press OK.
• MolMechanics/View Stack and look at the solutions ranked by energy by double clicking through the table.
• Compare your mutated structure with the crystal structure of PIM1 with the P123M mutation (PDB code 1yxs)