Using ferric-S-methyl-porphyrin as the prototype of heme-containing complexes, we address how to accurately and efficiently carry out density functional studies for systems of biological importance. Our results indicate that GGA and meta-GGA functionals bias the lower spin state by producing levitated frontier orbitals and often fail to provide a correct description of the ground spin state. Also, we propose composite double and triple zeta quality basis sets with polarization functions applied only to the transition metal and electro-negative atoms. Accurate structural and electronic properties including DFT reactivity indices have been obtained and significant gain in computational efficiency has been achieved.