The human immunodeficiency virus-type 1 (HIV-1) nucleocapsid (NC) protein is critical for the recognition and packaging of the viral genome and has been a potential target for the development of antiviral drugs. All retroviral NC proteins contain one or two copies of an invariant array of CCHC (Cys-X2-Cys-X4-His-X5-Cys) that are crucial for RNA genome recognition, packaging, and infectivity and have been proposed to function as zinc-binding domains. Although the solution structures of the NC protein with Zinc binding have been determined by experimental studies, the physiological relevance of zinc coordination has not been revealed. Here, we present the structural characteristics of the NCp7 protein with Zn and without Zn ions to investigate the coordination effect in the structural transitions upon inhibitory process by potential drugs by using molecular dynamics simulations with explicit water. For the elucidation of the structural and dynamic properties of the Zn-ligand binding domain in NCp7 protein, quantum mechanical calculations were executed to properly develop the force field for Zn. Upon ligand binding to NCp7 protein, correlation between experimental and computed dissociation constants will be discussed with the mechanistic variations for the ligand-binding and inhibition of NCp7 protein.