Generalized Born/Surface Area Model

The Generalized Born and Generalized Born/Surface Area Models in Molecular Mechanics... 

This combination of Equations [5] and [16] is called the Generalized Born/Surface Area model (GB/SA), and it is currently available in the Macro-ModeP computer package. The speed of the molecular mechanics calculations is not significantly decreased by comparison to the gas phase situation, making this model well suited to large systems. Moreover, the model takes account of some first-hydration-shell effects through the positive surface tension as well as the volume polarization effects. A selection of data for aqueous solution is provided later (Table 2), and the model is compared to experiment and to other models. Nonaqueous solvents have been simulated by changing the dielectric constant in the appropriate equations, 8 but to take the surface tension to be independent of solvent does not seem well justified. 

The generalized Born/surface area (GB/SA) model is a combination of the Born and SASA models. This method has been effective in describing the solvation of biomolecular molecules. It is incorporated in the MacroModel software package. 

It is important to emphasize that only the solvent-accessible surface area (SASA), the generalized Born/surface area (GB/SA), and the full AMI—SM2 models purport to address local, nonelectrostatic effects. There is no a priori reason to expect the remaining purely electrostatic models to correlate closely with experiment nevertheless, it is worthwhile to examine the cross-correlations. We will highlight some of the most interesting trends. 

Transferrin model compounds and 44 related iron(III) crystal structures were used to modify the AMBER force field for subsequent studies of ferric transferrin. Energy minimization was conducted both in vacuo and, more interestingly, with the generalized Born/surface area (GB/SA) continuum treatment described in Section 3.7 [548]. 

A series of continuum solvation models (SMx, x = 1-5) has been developed by Truhlar and co-worker (Cramer and Truhlar [79]), based on the Generalized Born/Surface Area (GB/SA) model (Still et al. [86]). Recall that in the GB approach the molecular shape is taken into account as the solute charge is distributed over a set of atom-centered spheres. For this GB/SA model, the polarization free energy is given by... 

Using partial atomic charges in eq. (14.59) is often called the generalized Bom model, which has been used especially in connection with force field methods in the Generalized Born/Surface Area (GB/SA) model. In this case, the Coulomb interaction between the partial charges (eq. (2.20)) is combined with the Bom formula by means of a function fy depending on the intemuclear distance and Born radii for each of the two atoms,and aj. 

The change in free energy for the transfer of a solute from an aqueous to an organic solvent can be computed using a continuum solvation model (the generalized Born/surface area, GB/SA) or a quantum mechanical model such as SMI, SM2, SMS,. . . , etc., where SM denotes solvation model. These methods are less CPU intensive than the molecular dynamics or Monte Carlo approaches described below. 

Both the united atom and all-atom AMBER parameter sets have been applied in simulations of the solvation free energies for several monosaccharides. The simulations were performed with the generalized Born surface-area-dependent (GB/SA) continuum water model, and gave rise to excellent agreement with experiment for example, ACo-G cp(.a- P) =(united atom), -0.12 (all-atom), and -0.34 kcal mol (experimental), and ACD-Man/)(cr->/ ) = 0.2,5 (united atom), 0.24 (all-atom), and 0.42 kcal mol (experimental). The good agreement obtained with the continuum water simulations suggests that discrepancies between the results obtained from explicit... 

Ghosh, A. Rapp, C.S. Friesner, R.A., Generalized Born model based on a surface area formulation, J. Phys. Chem. B 1998,102, 10983-10990... 

Models for which the parameterizations are based on the solvent accessible surface area (SASA) are widely known in literature.58 The nonpolar component of the free energy of solvation is described in these models as a polynomial of A , where A, is the SASA of the atom i. A very good example of such approach is the Surface Generalized Born/Nonpolar Model (SGB/NP), proposed by Gallicchio and Levy.83 The nonpolar contribution is expressed as ... 

We developed the Analytical Generalized Born plus Non-Polar (AGBNP) model, an implicit solvent model based on the Generalized Born model [37-40,44, 66] for the electrostatic component and on the decomposition of the nonpolar hydration-free energy into a cavity component based on the solute surface area and a solute-solvent van der Waals interaction free energy component modeled using an estimator based on the Born radius of each atom. 

Labute, P. (2008) The generalized Born/ volume integral implicit solvent model estimation of the free energy of hydration using London dispersion instead of atomic surface area./. Comput. Chem. 29, 1693-1698. 

The most rigorous dielectric continuum methods employ numerical solutions to the Poisson-Boltzmann equation [55]. As these methods are computationally quite expensive, in particular in connection with calculations of derivatives, much work has been concentrated on the development of computationally less expensive approximate continuum models of sufficient accuracy. One of the most widely used of these is the Generalized Born Solvent Accessible Surface Area (GB/SA) model developed by Still and coworkers [56,57]. The model is implemented in the MacroModel program [17,28] and parameterized for water and chloroform. It may be used in conjunction with the force fields available in MacroModel, e.g., AMBER, MM2, MM3, MMFF, OPTS. It should be noted that the original parameterization of the GB/SA model is based on the OPLS force field. 

Dielectric continuum models such as the Generalized Born Solvent Accessible Surface Area (GB/SA) model are, in conjunction with force fields, excellent tools for fast and reliable calculations of hydration energies and solvent effects on, e.g., conformational equilibria and ligand-receptor interactions. The performance for neutral solutes is very good, whereas calculations on ionic compounds are currently more problematic. A solution to these problems most probably requires force fields that include polarization effects. For optimal accuracy of calculations using a dielectric continuum model, it is a clear advantage if the model is parameterized for the particular force field used. 

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