ONIOM

The ONIOM approach (our Own N-layer Integrated molecular Orbital molecular Mechanics) developed by the Morokuma group takes an alternative approach to hybrid QM/MM. The distinct advantages of the ONIOM approach are that 

the entire system is referred to as the real space, and the model space is the region of the molecule that requires greater computational care. The computational 

It is important to recognize that the low level computation, and the low and intermediate level computations in a three-layer ONIOM, does not have to be MM. Any computational method can be used for any layer. For example, a three-layer ONIOM might use a semiempirical computation for the real system (5q), a DPT computation for the intermediate layer (Si), and a CASSCF computation for the high layer (82). 

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Dapprich S, 1 Komiromi, K S By un, K Morokuma and M J Frisch 1999. A New ONIOM Implementation in Gaussian 98. Part I. The Calculation of Energies, Gradients, Vibrational Frequencies and Electric Field Derivatives. THEOCHEM 461-462 1-21. 

W C, A Tempcz)rrk, R C Hawley and T Hendrickson 1990. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society 112 6127-6129. ensson M, S Humbel, R D J Froese, T Matsubara, S Sieber and K Morokuma 1996. ONIOM A Multilayered Integrated MO + MM Method for Geometry Optimisations and Single Point Energy Predictions. A Test for Diels-Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition. Journal of Physical Chemistry 100 19357-19363. 

Three such methods have been proposed by Morokuma and coworkers. The integrated MO + MM (IMOMM) method combines an orbital-based technique with an MM technique. The integrated MO + MO method (IMOMO) integrates two different orbital-based techniques. The our own n-layered integrated MO and MM method (ONIOM) allows for three or more different techniques to be used in successive layers. The acronym ONIOM is often used to refer to all three of these methods since it is a generalization of the technique. 

The concept has been generalized in the ONIOM method to include several layers, for example using high level ab initio (e.g. CCSD(T)) in the central part, lower-level electronic structure theory (e.g. MP2) in an intermediate layer and a force field to treat the outer layer. 

A thorough computational study of this process has been carried out using B3LYP/ONIOM calculations.31 The rate-determining step is found to be the formation of the rhodium hydride intermediate. The barrier for this step is smaller for the minor complex than for the major one. Additional details on this study can be found at ... 

Abstract ONIOM is a flexible hybrid scheme that can combine the most suitable computational... 

Keywords ONIOM, QM/MM protein environmental effects, Bacteriorhodopsin, Methane,... 

In the present article, we will at first briefly overview the ONIOM methodology, with an illustration of a benchmark test of a three-layer ONIOM(QM QM MM) method, which we consider a method of future. Then we will review our recent studies of biocatalysis in which we used the ONIOM(QM MM) method to examine the effects of protein environments on the mechanisms of enzymatic reactions, with an emphasis on metalloenzymes. 

The accuracy of the ONIOM method is defined as the error of ONIOM relative to the target calculation ... 

Errrea IOM depends critically on the partitioning of the model system and the reliability of the low-level method used in ONIOM. The accuracy of any ONIOM combination can be tested using the S-values, which are defined as ... 

With these definitions of the S-values, the ONIOM energy can be written as ... 

ONIOM can combine two MO levels like ONIOM(QM QM), which is a unique feature that is not available to QM/MM methods. However, the most popular combination is ONIOM(QM MM), combining QM with MM. This is essentially equivalent to generic QM/MM. However, there are some subtle cancellation or double-counting differences for the case where a covalent bond is cut. For this, we refer to a detailed discussion published elsewhere [8], QM MM or QM/MM applications have typically been used without appropriate accuracy or S-value tests, as the benchmark full QM calculation for the real system is often impossible. In Section 2.2.2, we will examine one such test in detail. 

The 3-layer combination, ONIOM(QM QM MM), shown in Figure 2-1, is also a unique combination not available in the generic QM/MM approach and we recommend this method strongly, as the border between QM and MM regions is pretty far away form the active part of the system and the effects of scaling is... 

Figure 2-1. Representation of the three-layer ONIOM method (Reprinted with permission from Morokuma et al. [11]. Copyright 2006 American Chemical Society.)...

Benchmark Test of Three-Layered ONIOM Method... 

To illustrate the potential of the three-layer ONIOM method, we show results from a systematic comparison of three- and two-layer ONIOM methods with full QM benchmark calculations [11], The system studied is a zwitterionic peptide, NH3+—CHnBu—CO—NH—CH2—CO—NH—CH Bu—COO-, and the partition scheme illustrated in Figure 2-2 is used. In this partition, both model and mid... 

ONIOM combination3 Estimated Costb Atoms in the model system only All atoms in the real system ... 

Table 2-2. 1-, 2- and 3-layered ONIOM calculations for the deprotonation energy (in kcal/mol) of NH —CnBuH — CO—NH—CH2 — CO—NH — CHnBu — COO- system using the optimized geometries by the respective methods (Reprinted with permission from Morokuma et al. [11]. Copyright 2006 American Chemical Society.)... 

To summarize, we have systematically tested all possible three- and two-layer ONIOM combinations of high-level QM (HQ=B3LYP/6-31G ), low-level QM (LQ=AM1), and MM (Amber) for the deprotonation energy and structure of a test molecule, an ionic form of a peptide. We find the errors introduced in the ONIOM approximation, in comparison with the target HQ (or HQ HQ HQ) calculation, generally increases in the order ... 

There is no well-defined way of calculating deprotonation energy with Amber. However, this does not matter as it totally cancels out in ONIOM by taking the difference between the real and model system. 

For realistic systems, the HQ calculation for the middle system and the LQ calculation for the real system can be expensive we have no choice but using MM in the real system. The AMI as the highest level (semiempirical QM/MM) has too large an error to be useful, while also a QM-MM boundary close to the region of the action, in ONIOM(QM MM MM), produces large errors. 

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