Calmodulin (CaM) is a highly conserved 17 kDa eukaryotic protein that can bind specifically to over 100 protein targets in response to a Ca2+ signal. Present study was planned to mutate the crucial residues of N-terminal lobe, central helix, and C-terminal lobe that play important roles in activating and binding of enzymes. In all, 10 mutations were carried out in the predicted 3D structure of calmodulin using the computer program MODELLER 6v2. Mutations at specific residues in both the N-terminal and C-terminal regions resulted in the change in the interaction pattern of these amino acids. No significant change was however predicted by mutating amino acid residues in the central helix. The predicted alteration in the interaction of specific amino acids may either alter the binding affinity with calcium ions or decrease the ability of calmodulin to activate the specific enzymes. (C) 2004 Elsevier Inc. All rights reserved.