Polarized Protein-Specific Charge

The contribution from the base charge is removed from the standard ESP, which is usually obtained from quantum mechanical calculations. Instead of fitting the total atomic charge directly, only the perturbation is fitted to the residual ESP. The figure-of-merit function is now written as 

It then follows the same way as that in the original RESP fit except that a different way to assign the weighting factor for each atom is employed. 

In RESP fit, restraint that keeps the atomic charge near zero are applied to each atom with a uniform weighting factor. In this fitting method, different weighting factors are assigned to the atoms, which are reversely proportional to the square of the base charges. 

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Ji, C., Mei, Y., and Zhang, J. Z. H. [2008], Developing polarized protein-specific charges for protein dynamics MD free energy calculation of pka shifts for asp26/asp20 in thioredoxin, Biophysical Journal 95, 3, pp. 1080-... 

Both of the above approaches rely in most cases on classical ideas that picture the atoms and molecules in the system interacting via ordinary electrical and steric forces. These interactions between the species are expressed in terms of force fields, i.e., sets of mathematical equations that describe the attractions and repulsions between the atomic charges, the forces needed to stretch or compress the chemical bonds, repulsions between the atoms due to then-excluded volumes, etc. A variety of different force fields have been developed by different workers to represent the forces present in chemical systems, and although these differ in their details, they generally tend to include the same aspects of the molecular interactions. Some are directed more specifically at the forces important for, say, protein structure, while others focus more on features important in liquids. With time more and more sophisticated force fields are continually being introduced to include additional aspects of the interatomic interactions, e.g., polarizations of the atomic charge clouds and more subtle effects associated with quantum chemical effects. Naturally, inclusion of these additional features requires greater computational effort, so that a compromise between sophistication and practicality is required. 

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