The ONIOM Method and Its Applications.

Solvent effects on the excited state properties of 2-aminopurine—a theoretical study by the ONIOM and Supramolecular method

Calculation of the properties of acid sites of the zeolite ZSM-5 using ONIOM method

The ONIOM method was used to reproduce geometrical parameters, atomic charges, dipole moment for α and β L-Fucopyranose which are biological interest molecules. The results of ONIOM(MP2/HF) and ONIOM(B3LYP/HF) calculations were compared to the values obtained by means of its corresponding theoretical levels MP2, DFT and RHF with 6-31G* bases set, using GAUSSIAN 98 software.

L-6-Hydroxynicotine oxidase (LHNO) is a member of monoamine oxidase (MAO) family and catalyzes conversion of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during bacterial degradation of nicotine. Recent studies indicated that the enzyme catalyzes oxidation of carbon-nitrogen bond instead of previously proposed carbon-carbon bond. Based on kinetics and mutagenesis studies, Asn166, Tyr311, and Lys287 as well as an active site water molecule have roles in the catalysis of the enzyme. A number of studies including experimental and computational methods support hydride transfer mechanism in MAO family as a common mechanism in which a hydride ion transfer from amine substrate to flavin cofactor is the rate-limiting step. In this study, we formulated computational models to study the hydride transfer mechanism using crystal structure of enzyme-substrate complex. The calculations involved ONIOM and DFT methods, and we evaluated the geometry and energetics of the hydride transfer process while probing the roles of active site residues. Based on the calculations involving hydride, radical, and polar mechanisms, it was concluded that hydride transfer mechanism is the only viable mechanism for LHNO.

The two‐layer ONIOM method is applied for description of Mo‐methylidene center on silica, which is the active site of olefin metathesis. Two clusters of different size are employed to model the silica surface. For the larger one, two differently defined inner layers (the model systems) are tested. In all the calculations, the B3LYP functional is adopted for the inner layer, while the Hartree–Fock method or the local density approximation (SVWN5 functional) is used for the treatment of the real system. Based on the reference results obtained for the real system from the B3LYP calculations, it is concluded that both B3LYP:HF and B3LYP:SVWN5 schemes are suitable for proper description of the geometry of the Mo center and its activity in ethene metathesis. The former combination is a little better choice, however. It is also shown that the inner layer, including the third coordination sphere of molybdenum, is large enough to obtain satisfactory results. On the other hand, the relative energies and some geometrical parameters of the active site are dependent on the size of the entire system studied. The sensitivity of the geometrical parameters and reaction energies to the changes of the scale factor g, involved in the ONIOM scheme, is studied as well. It is concluded that the link atom distance is not crucial for obtaining correct results. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

Toward high-level theoretical studies on the reaction kinetics of PAHs growth based on HACA pathway: An ONIOM[G3(MP2,CC)//B3LYP:DFT] method developed

Many coupled quantum mechanical/molecular mechanical (QM/MM) methods employ disjoint sub domains for the MM and QM regions together with link atoms to ameliorate the effects of severing covalent bonds that straddle the QM/MM interface. In the context of simulations of mechanical properties, this can be problematic because the interactions bet ween the subdomains are then modeled by bonds involving link atoms and such bonds typically do not closely resemble those of the original system. In this paper we consider two coupling schemes that employ overlapping domains. The first is the ONIOM schem e of Morokuma et al. that includes an MM treatment of the entire system together with QM corrections for key subdomains. The second is a new approach that we will refer to as the overlapping domain link atom (ODLA) method. This method involves only a min imal overlap between the QM and MM subdomains. One important advantage of the ODLA scheme as compared to the ONIOM method is that, within the region that is treated entirely by QM methods, chemical interactions can be modeled for which reliable MM potenti als are unavailable. Results of fracture studies of defected graphene sheets obtained with the ONIOM and ODLA methods are compared to benchmark results obtained by an entirely QM treatment. Both coupling methods perform well and the two coupling methods display very close agreement.

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bondinteractions is discussed using the atoms in molecules (AIM)analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide information that will aid in the design of much improved HIV-1 PR antiviral drugs.

Ti atom in MFI zeolite framework: a large cluster model study by ONIOM method

The reactivity of H2O and the Si-terminated silicon carbide surface (001) was investigated on the triplet potential energy surface with the combined first principle and molecular mechanics ONIOM(CASSCF:AM1:UFF) method for the (SiC)192·H2O model. It was found that the H2O molecule and the surface can form three physisorption complexes and follow five reaction paths to produce eight products, in which there are five main products having necessary energy barriers less than 300 kJ mol−1. Compared with that on the C-terminated surface, the interaction with the Si-terminated surface has stronger physisorption energy, smaller lowest necessary energy barrier, more main and more stable products.

As quantum chemistry plays a more and more central role in many complicated chemical problems, it has become necessary to obtain accurate results for large molecular systems. Conventional quantum chemistry methods are either too expensive to apply to large systems or too approximate for the results to be reliable, and they fail to satisfy this requirement. A variety of different approaches is being developed with the aim of achieving this goal: local correlation methods; divide-and-conquer methods; linear-scaling density functional methods based on the fast multipole and other approximations; effective potential methods; and hybrid methods. ONIOM (our N-layered integrated molecular orbital plus molecular mechanics method), developed by the authors, is a hybrid method in which a large molecular system is divided into onion-skin-like layers, and different quantum chemistry/molecular mechanics methods are used for different parts of the system; the results are combined to extrapolatively estimate the results of high-level calculation for the real system. Several applications of ONIOM will be discussed.

Assessment of mixed basis set and ONIOM methods on the activation energy of ring opening reactions of substituted cyclobutenes

We demonstrate that the ONIOM method can be used to optimize a conical intersection between the ground and first excited-state potential energy surfaces of previtamin D (precalciferol), with excitation localized in a small part of the molecule: the hexatriene chromophore. These calculations were up to 100 times faster with little loss of accuracy compared to a full non-ONIOM Target calculation. The most accurate ONIOM method combination was CASSCF/4-31G//ROHF/STO-3G(Triplet): in comparison to the Target (CASSCF/4-31G), bond lengths and angles in the hexatriene model region were calculated to within 0.02 A and 0.7 degrees , respectively, and the energy difference between the conical intersection and nearest associated S 1 minimum to within 0.5 kcal x mol (-1). All of the low-level methods selected produced accurate geometries, including the UFF molecular mechanics and AM1 semiempirical methods, suggesting a cheap and efficient way of initially optimizing conical intersections geometries. Furthermore, ONIOM allows for an assessment of the localization of excited states, providing some fundamental insight into the physical processes involved.

The inability to describe charge redistribution effects between different regions in a large molecule can be a source of error in an ONIOM hybrid calculation. We propose a new and an inexpensive method for describing such charge-transfer effects and for improving reaction energies obtained with the ONIOM method. Our method is based on matching the electrostatic potential (ESP) between the model system and the real system. The ESP difference arising due to charge redistribution is overcome by placing an optimum one electron potential at a defined buffer region. In our current implementation, the link atom nuclear charge is optimized iteratively to produce a model low ESP distribution equal to that in the real low calculation. These optimum charges are relatively small in magnitude and corroborate physical intuition. This new ESP-ONIOM-CT method is independent of any arbitrary definition of charges, is defined on the basis of a physical observable, and is less basis set dependent than previous approaches. The method is easily extended for studying reactions involving multiple link atoms. We present a thorough benchmark of this method on test sets consisting of one- and two-link atom reactions. Using reaction energies of four different test sets each with four different combinations of high:low levels of theory, the accuracy of ESP-ONIOM-CT improved by 40-60% over the ONIOM method.

Theoretical investigation on nevirapine and HIV-1 reverse transcriptase binding site interaction, based on ONIOM method