Generalized Bom

It is often the case that the solvent acts as a bulk medium, which affects the solute mainly by its dielectric properties. Therefore, as in the case of electrostatic shielding presented above, explicitly defined solvent molecules do not have to be present. In fact, the bulk can be considered as perturbing the molecule in the gas phase , leading to so-called continuum solvent models [14, 15]. To represent the electrostatic contribution to the free energy of solvation, the generalized Bom (GB) method is widely used. Wilhin the GB equation, AG equals the difference between and the vacuum Coulomb energy (Eq. (38)) ... 

Totrov, M. Accurate and efficient generalized Bom model based on solvent accessibility derivation and application for logP octanol/water prediction and flexible peptide docking, f Comput. Chem. 2004, 25, 609-619. 

Feig M, Onufriev A, Lee MS, Im W, Case DA, Brooks CL III (2004) Performance comparison of generalized bom and poisson methods in the calculation of electrostatic solvation energies for protein structures. J Comput Chem 25 265—284. 

Im W, Lee MS, Brooks CL III (2003) Generalized Bom model with a simple smoothing function. J Comput Chem 24 1691-1702. 

Kikuchi, O., T. Matsuoka, H. Sawahata, and O. Takahashi. 1994. Ab Initio Molecular Orbital Calculations Including Solvent Effects by Generalized Bom Formula. Conformation of Zwitterionic Forms of Glycine, Alanine and Serine in Water, J. Mol. Struct. (Theochem) 305, 79-87. 

Nymeyer, H. Garcfa, A. E., Simulation of the folding equilibrium of o-helical peptides a comparison of the generalized Bom approximation with explicit solvent, Proc. Natl Acad. Sci. USA. Nov 2003,100,13934-13939. 

X. Xou, Y. Sun, and I. Kuntz, Inclusion of solvation in ligand binding free energy calculations using the generalized-Bom model, J. Am. Chem. Soc. 121 8033 (1999). 

S. C. Tucker and D. G. Truhlar, Generalized Bom fragment charge model for solvation effects as a function of reaction coordinate, Chem. Phys. Lett. 157 164 (1989). 

In the generalized Bom model, the solvent polarization energy, Gpoi, is approximated by the following equation... 

The incorporation of the generalized Bom model into free energy calculation methods using FEP/TI and A-dynamics was carried out by Banba and Brooks.81 They define the electrostatic solvation energy for the hybrid system as follows... 

D. Bashford and D. A. Case, Generalized Bom models of macromolecular solvation... 

C. S. Rapp and R. A. Friesner, Prediction of loop geometries using a generalized Bom... 

E-B. A model solution to the electrostatic problem, e.g., the Generalized Bom Approximation or a conductor-like screening solution. 

The generalized Bom model (GBM) can be regarded as a special case of the preceding procedures the reaction field is expressed in terms of a multi-center monopole representation of the solute molecule, using the Bom formula, Eq. (32).l3 ,6, 3 "5 The centers are the atomic nuclei. The results are quite sensitive to the method used to calculate the atomic charges Cramer and Truhlar, who have applied the GBM approach extensively13,16,107 use their Class IV charges for this purpose.16,107,116 Various techniques have been utilized to determine the radii.16,95,101,107... 

Kang, X. S., Shafer, R. H., and Kuntz, I. D. 2004. Calculation of Ligand-nucleic Acid Binding Free Energies with the Generalized-Bom Model in dock . Biopolymers, 73, 192. 

In order to solve die Poisson equation for an arbitrary cavity, recourse to numerical methods is required. An altemative approach that has seen considerable development involves computing die polarization free energy using an approximation to the Poisson equation that can be solved analytically, and diis is the Generalized Bom (GB) approach. As its name implies, the GB method extends the Born Eq. (11.12) to polyatomic molecules. The fundamental equation of the GB method expresses the polarization energy as... 

In the majority of continuum solvation models incorporating a surface-tension approach to estimating the non-electrostatic solvation components, the index k in Eq. (11.22) runs over a list of atom types, and die user assigns the appropriate type to each atom of the solute. This is particularly straightforward for MM models, like the Generalized Bom/Surface Area (GB/SA) model (Still el al. 1990 see also Best, Merz, and Reynolds 1997), since atom types are already intrinsic to the force field approach. This same formalism has been combined with the CHARMM and Cornell et al. force fields (see Table 2.1) to define GB models for proteins and nucleic acids (Dominy and Brooks 1999 Jayaram, Sprous, and Beveridge 1998). Considering this approach applied within the QM arena, the MST-ST models of Orozco and Luque have been the most extensively developed (see, for instance, Curutchet, Orozco, and Luque 2001). 

Generalized Bom models do not suffer from the multiple cavity problem, which is a particular advantage of that methodology. However, initial studies have suggested that... 

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