CHARMm force fields link atoms

In an attempt to aid interpretation of the IR spectrum of MbCO we decided to model the full protein by use of a hybrid quantum mechanics/molecular mechanics approach (QM/MM), to evaluate changes in the CO stretching frequency for different protein conformations. The QM/MM method used [44] combines a first-principles description of the active center with a force-field treatment (using the CHARMM force field) of the rest of the protein. The QM-MM boundary is modeled by use of link atoms (four in the heme vinyl and propionate substituents and one on the His64 residue). Our QM region will include the CO ligand, the porphyrin, and the axial imidazole (Fig. 3.13). The vinyl and propionate porphyrin substituents were not included, because we had previously found they did not affect the properties of the Fe-ligand bonds (Section 3.3.1). It was, on the other hand, crucial to include the imidazole of the proximal His (directly bonded to the... 

It is interesting to compare the possibilities and errors of different hybrid QM/MM schemes. The careful examination and comparison of link atom and LSCF techniques was performed in Ref. [128] using the CHARMM force field [114] and the AMI method [143] as a quantum chemical procedure. In the case of the link atom procedure two options were used QQ - the link atom does not interact with the MM subsystem and HQ - link atom interacts with all MM atoms. The main conclusion of this consideration is that the LSCF and the link atom schemes are of similar quality. The error in the proton affinity determination induced by these schemes is several kcal/mol. It is noteworthy that all the schemes work rather badly in description of conformational properties of n-butane. The large charge on the MM atoms in the proximity of the QM subsystem (especially on the boundary atom) cause significant errors in the proton affinity estimates for all methods (especially, in the case of the LSCF approach where the error can be of tens of kcal/mol). This is not surprising since the stability and transferability of intrabond one- and two-electron density matrix elements Eq. (19) is broken here. It proves that the simple electrostatic model is not well appropriate for these schemes and that a detailed analysis of the... 

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