Protein kinases in general are known to be very flexible macromolecules. In this article, the conformational plasticity of the ATP binding site in cyclin dependent kinases is analyzed. Movement of the two lysine residues lining the ATP binding site are shown to play a major role in the conformational variability of the site. Linear models are developed to identify and quantify ligand properties that maximally influence the lysine side chain conformations. A few simple properties of the ligands are shown to account for more than 70% of the variation in the lysine conformations. The results are validated using test data and molecular simulation studies. Illustrative applications of the results of this analysis to finding the appropriate crystal structure for molecular docking and binding mode predictions of novel ligands are provided. This work provides a new approach to quantify ligand-induced conformational changes in the active sites of flexible proteins and to find the appropriate crystal structure for docking novel ligands.