Human big conductance Ca²⁺ and voltage gated potassium channels¹ (hBK) play an important role in the repolarization of the membranes and are putative drug targets for cardiovascular, respiratory and urological diseases. Human Bestrophins1² (hBest1) are suggested to function as Cl^– channels, having Ca²⁺ sensitivity and are associated with age-related macular degeneration, particularly with Best vitelliform macular distrophy. The crystal structures for both channels are unknown. However they share the known calcium-binding motif pattern DDD-x-[D,E]. We have used bioinformatics and molecular simulation approaches to construct models of putative calcium-binding domains in hBK and hBest1 channels. Models could help to rationalize the available experimental data and to plan new experiments in order to understand the physiological role of these classes of channels. The search of this calcium-binding motif in the Swiss-Prot database by means of Prosite produced a high number of results. However, only a few of them correspond to proteins, which are actually known to bind calcium. Among them just the human Thrombospondin-1³ (hTSP-1) has the three-dimensional (3-D) structure available. Therefore human TSP-1 calcium-binding domain was used as a template for the modeling the putative calcium-binding domains of hBK and hBest1. Molecular dynamics simulations were then carried out on both models to evaluate the thermodynamic stability and to study the dynamical properties of both calcium-binding domains.