The geometries of various conformations of tetraamino-p-tert-butylthiacalix[4]arene (L) were optimized using the semiempirical AM1, HF/3-21G, density functional theory at B3LYP/6-31G(d) level and various two-layered ONIOM(B3LYP/6-31G(d):MO) methods. In decreasing order, the relative stability of four characteristic conformations obtained from different MO calculations is cone, partial cone, 1,3-alternate and 1,2-alternate conformers. The B3LYP/6-31G(d) and two-layered ONIOM (B3LYP/6-31G(d):AM1) optimized geometries of 1,3-alternate (0101-CCCC) show excellent agreement with the X-ray crystallographic structure. The geometry optimization of various protonated species of L and its zinc complex were carried out at ONIOM (B3LYP/6-31G(d):MNDO), ONIOM (B3LYP/6-31G(d):PM3), ONIOM (B3LYP/6-31G(d):AM1) and ONIOM (B3LYP/6-31G(d):AM1) levels of theory. The energies of protonation, preorganization of L and complexation with zinc were derived from total energies at various ONIOM(B3LYP/6-31G(d):MO) levels. The electrostatic potential surfaces of cone (0000-CCCC) and 1,3-alternate (0101-CCCC) conformers were presented.