Link-atom method

A subtle but key difference in the methodologies is that the orbital containing the two electrons in the C-X bond is frozen in the LSCF method, optimized in the context of an X-H bond in the link atom method, and optimized subject only to the constraint that atom C s contribution be a particular sp hybrid in the GHO method. In the link atom and LSCF methods, the MM partial charge on atom C interacts with some or all of the quantum system in the GHO method, it is only used to set the population in the frozen orbitals. 

For the majority of enzyme-catalysed reactions, covalently bonded parts of the system must be separated into QM and MM regions. There has been considerable research into methods for QM/MM partitioning of covalently bonded systems. Important methods include the local self-consistent field (LSCF) method,114115 and the generalized hybrid orbital (GHO) technique.116 Alternatively a QM atom (or QM pseudo-atom) can be added to allow a bond at the QM/MM frontier for example, the link atom method or the connection atom method. 

Amara P, MJ Field (2003) Evaluation of an ab initio quantum mechanical/molecular mechanical hybrid-potential link-atom method. Theor. Chem. Acc. 109 (1) 43—52... 

Das D, KP Eurenius, EM Billings, P Sherwood, DC Chatfield, M Hodoscek, BR Brooks (2002) Optimization of quantum mechanical molecular mechanical partitioning schemes Gaussian delocalization of molecular mechanical charges and the double link atom method. J. Chem. Phys. 117 (23) 10534-10547... 

The dummy junction atom or link atom approach introduces so-called link atoms to satisfy the valence of the atoms on the QM side of the QM/MM interface. Usually this atom is a hydrogen, but other atom types have also been used, e.g. halogens such as fluorine or chlorine. The link atom method can be used with both the Warshel-type QM/MM methods and ONIOM methods. The link atom method has been criticised because it introduces extra unphysical atoms to the system, which come with associated extra degrees of freedom. Another problem is that a C-H bond is clearly not chemically exactly equivalent to a C-C bond. Despite these problems, the simplicity of the link atom method means that it is used widely in the QM/MM modelling of proteins and other biological molecules. ... 

Another problem lies in the region between QM and MM. Considerable debate has arisen when the partitioning between the two regions cuts across covalent bonds [58,62,63]. The most common method in modeling this middle space is to use the link atom method. It consists of adding QM hydrogen atoms in order to fill the free valencies of the QM atoms that are connected to the atoms described by MM. These dummy atoms are explicitly treated during the QM calculations but do not interact with the MM atoms. Whether or not these link atoms should interact via Coulombic interactions is still open to debate. 

More sophisticated examples of such expressions are used in Pople s Gl, G2 and G3 theories.162-164 In the onion approaches, the calculated structure of the lower level is used as a constraint upon the higher level of theory. The breaking of covalent bonds between the model and the real system is treated by replacing the corresponding atom in the real system with a hydrogen atom in the model system, much like the link atom method. The coordinates of the new... 

Figure 2 A schematic diagram of the link atom method of Singh and Kollman [16] and Field et ainn...

Conceptually the hybrid orbital approach is to be preferred over the link atom method as no unphysical atoms are introduced into the system. Undoubtedly the HO method will become more popular but, as we shall see in section 4, link atoms have been the most widely used when studying macromolecular systems, in large part because they are simpler to implement. 

Of the three types of boundary treatment, the link atom method is the simplest both conceptually and in practice, and is hence the most widely used. The boundary atom and in particular the frozen orbital methods can potentially achieve higher accuracy but require careful a priori parametrization and bear limitations on transferability (Senn and Thiel 2009). 

Figure 2 Two alternative methods to treat the junction between the QM and MM regions. On the left, the link atom method is represented where the dummy atom is a QM hydrogen placed along the QM-MM bond. On the right is the single hybrid orbital model where there is a single hybrid orbital along the QM-MM bond...

An important aspect of the formation of a hybrid potential is how to handle the covalent bonds between atoms that are described with different potentials, that is, the bonds existing at the interface of the QM and MM regions. Several methods have been proposed to deal with this problem, including the simple link-atom method (Field et al. 1990), the sophisticated hybrid-orbital technique (Ferre et al. 2002), and the pseudo-bond approach (Zhang et al. 1999). 

Here, the classical link-atom method was introduced as a typical example. The link atoms as shown inO Fig. 52.14 are treated exactly like QM hydrogen atoms in the QM/MM scheme and they are invisible to the MM atoms because no interactions between the link atoms and the MM atoms are calculated. Each bond that crosses the boundary between the two regions must... 

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