Premium
DFT calculations and docking simulations of heme derivatives
Author(s) -
Correa Jose,
Rosales Martha C,
Flores Cesar,
Trujillo Jose
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a669-d
Subject(s) - chemistry , homo/lumo , heme , docking (animal) , substituent , aniline , density functional theory , protein data bank (rcsb pdb) , stereochemistry , polar effect , computational chemistry , electron density , photochemistry , enzyme , molecule , electron , organic chemistry , medicine , physics , nursing , quantum mechanics
DFT calculations and docking simulations of heme derivatives The molecular geometry of the heme derivatives was optimized by using DFT calculations at B3LP/3‐21G* level and their HOMO‐LUMO energies were calculated at B3LYP/6‐31G* level. Then, these heme derivatives were docked on CYP2B4 (without original heme). Finally, aniline and N‐methylaniline were docked on CYP2B4 (pdb: 2bdm ) with the different heme derivatives. The results showed that the LUMO density at the iron and sp3 carbons of the heme increases when its vinyl and propionic groups are substituted by electron withdrawing groups, while their HOMO density increases when electron donating groups are substituted in the same positions. When the propionic groups are modified with electron withdrawing or electron donating groups, the electronic density is maintained over their sp3 carbons, avoiding electron transfer from the substituent to the iron atom. Consequently, it is possible that different interactions also exist between the substrate and the sp3 carbons. The docking simulations showed that the heme derivatives are recognized in the same site where is place the heme original on CYP2B4 at Cys436. Thus results let us to obtain several different CYP2B4s. On these enzymes, the aniline and N‐methylaniline were docked showed that their affinities increase when CYP2B4 has the heme which showed the highest LUMO energies on porphyryn skeleton by DFT studies. The results suggest that CYP450 activity could be improved by changing the modifies hemes in experimental models to carry out more efficiently and faster the metabolism assays in vitro than original CYP2B4.