To investigate the effect of trifluoperazine(TFP) on $Ca^{2+}$-binding process of calmodulin (CAM), molecular dynamics simulations were carried out with CVFF system of program, DISCOVER and the environment was modeled with a distance-dependent dielectric permittivity. By using interactive computer graphics, seven models of CAM were constructed based on sequential $Ca^{2+]$-occupancy in N-terminal domain and TFP-occupancy. These models were also built from such a premise that TFP can participate in $Ca^{2+}$-binding process of N-terminal domain. The $Ca^{2+}$-dependence of TFP-binding provides an information about the location of the $Ca^{2+}$-binding sites that affect TFP-binding. Loop-selectivity of the first $Ca^{2+}$ in N-terminal domain is determined by the difference between $Ca^{2+}$-affinity of two EF hands. In the analysis of resulting structure, TFP-accessibility for selected residues as hydrophobic pocket led to the conclusion that one $Ca^{2+}$ must be bound to EFII for TFP to bind to CAM. The first $Ca^{2+}$ in N-terminal domain binds to EFII better than EFI. In cooperativity, the measurement of the distance between each center of mass of two EF hand in the model systems provides an insight that electrostatic attraction between each $Ca^{2+}$ and four surface residues of the other loop(EACL) plays a dominant role. TFP increases EACL in the second $Ca^{2+}$-binding of N-terminal domain of CAM. In particular, in ASP 20, ASP 56, ASP 58. As the result of the effect, the second $Ca^{2+}$-affinity and cooperativity in $Ca^{2+}$-binding of N-terminl domain increase.