ONIOM methods

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. 

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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. 

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... 

The present chapter reviews applications in biocatalysis of the ONIOM method. The focus is on studies performed in our research group, in most cases using the two-layer ONIOM(QM MM) approach as implemented in Gaussian [23], The studied systems include methane monooxygenase (MMO), ribonucleotide reductase (RNR) [24, 25], isopenicillin N synthase (IPNS) [26], mammalian Glutathione peroxidase (GPx) [27,28], Bi2-dependent methylmalonyl-CoA mutase [29] and PLP-dependent P-lyase [30], These systems will be described in more detail in the following sections. ONIOM applications to enzymatic systems performed by other research groups will be only briefly described. 

Despite the availability of fast computers and efficient codes for accurate quantum chemistry calculations, it is not likely in the near future that we will be able to study chemical reactions in proteins taking all the proteins atoms into quantum mechanical calculations. Hybrid methods in which different parts of large molecular systems are treated by different theoretical levels of methods are likely to play a key role in such studies for the coming decade or more. The ONIOM method we have developed is a versatile hybrid method that allows combining different quantum mechanical methods as well as molecular mechanics method in multiple layers, some features of... 

The success in a simple model system encouraged Feldgus and Landis to study the fuller DUPHOS-based system for enantioselective hydrogenation (as defined in Fig. 31.9) [45]. ONIOM methods were required because of the level of complexity a core of the rhodium-complexed atoms was treated by DFT at B3LYP level, the core organic atoms at Hartree-Fock level, and the remainder by... 

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