We analyze the apo and holo calmodulin (CaM) structures by sequentiallyinserting a perturbation on every residue of the protein, and monitoring thelinear response. Residue crosscorrelation matrices obtained from 20 ns longmolecular dynamics simulation of the apo-form are used as the kernel in thelinear response. We determine two residues whose perturbation equivalentlyyields the experimentally determined displacement profiles of CaM, relevantto the binding of the trifluoperazine (TFP) ligand. They reside onstructurally equivalent positions on the N- and C-terminus lobes of CaM, andare not in direct contact with the binding region. The direction of theperturbation that must be inserted on these residues is an important factorin recovering the conformational change, implying that highly selectivebinding must occur near these sites to invoke the necessary conformationalchange.
