Nanobiotechnology for health-care 

The effect of protein structure on O2 binding to heme: the hybrid QM/MM study.
Havrylov V.M.1, Afanasieva T.V.2, Mamilov S.O.3 
1 Taras Shevchenko University of Kyiv, Glushkova Avenue 4G, Kyiv-03187,
Ukraine.
2 Physical Electronics Department, Institute of Physics of the NAS of Ukraine. Prospect Nauki, 46, Kyiv-03039, Ukraine. 
E-mail: tetiana.v.afanasieva@gmail.com
 3Institute of Applied Problems of Physics and Biophysics of the NAS of Ukraine.
Vasylia Stepanchenka St., 3,  Kyiv-03142, Ukraine.

The mechanism of the photodissociation of oxyhemoglobin is debated for years due to its exceptional biologically importance. The binding of oxygen to the Fe-porphyrin complex involves structural changes in the protein. The effect of proximal histidines has been well established for the heme oxygen affinity. In contrast, the impact of peripheral residues, heme isomers and structure distortions on oxygen binding is still being actively investigated. The existence of a hydrogen bond between distal histidine and dioxygen has been established by experiment [1]. 
We simulated the effect of hemoprotein structure on oxygen binding using a hybrid quantum mechanical-molecular mechanical (QM/MM) method and embedded clusters - SIMOMM (Surface Integrated Molecular Orbital Molecular Mechanics) with GAMESS/TINKER software [2]. Density functional theory method and all-electron 6-31G(p,d) basis set with p, d polarization functions were used for the QM region. The MM region was completely optimized using MM3 parameters. 
The binding energies of O2 were calculated for different models of active sites for α and β subunits. Correspondent vibrational spectra were obtained and compared with the experiment. The effects of peripheral residues on oxygen binding energies and vibrational spectra are discussed.  

1.	Kepp K.P., Dasmeh P. Effect of distal interactions on O2 binding to heme // Phys. Chem. B.-2013.-117, N 14.-P. 3755–3770.
2.	Schmidt M. W. et al. GAMESS, The General Atomic and Molecular Electronic Structure System // J. Comput. Chem.-1993.-14.-P. 1347-1358.