Macromolecular solvation energy

M. K. Gilson and B. Honig, Proteins, 4,7 (1988). Calculation of Total Electrostatic Energy of a Macromolecular System Solvation Energies, Binding Energies, and Conformational Analysis. 

Gilson, M. K., and Honig, B. (1988). Calculation of the total electrostatic energy of a macromolecular system Solvation energies, binding energies, and conformational analysis. Proteins 4(1), 7-18. 

The other major energetic contributions to macromolecular solvation are from the VDW interactions and the hydrophobic effect. The former favors good solvent packing around a molecule, and will tend to oppose the effect of intramolecular VDW interactions. The hydrophobic effect drives nonpolar groups away from the solvent. These two interactions are combined in continuum solvent models into a surface free energy description, where the exposure of a certain solvent accessible area A of a molecule requires an energy = yA. The... 

It is possible to go beyond the SASA/PB approximation and develop better approximations to current implicit solvent representations with sophisticated statistical mechanical models based on distribution functions or integral equations (see Section V.A). An alternative intermediate approach consists in including a small number of explicit solvent molecules near the solute while the influence of the remain bulk solvent molecules is taken into account implicitly (see Section V.B). On the other hand, in some cases it is necessary to use a treatment that is markedly simpler than SASA/PB to carry out extensive conformational searches. In such situations, it possible to use empirical models that describe the entire solvation free energy on the basis of the SASA (see Section V.C). An even simpler class of approximations consists in using infonnation-based potentials constructed to mimic and reproduce the statistical trends observed in macromolecular structures (see Section V.D). Although the microscopic basis of these approximations is not yet formally linked to a statistical mechanical formulation of implicit solvent, full SASA models and empirical information-based potentials may be very effective for particular problems. 

Tel. 617-495-4018, fax 617-495-1792, e-mail karplus huchel.bitnet Molecular dynamics package using Chemistry at Harvard Macromolecular Mechanics force field. Extensive scripting language for molecular mechanics, simulations, solvation, electrostatics, crystal packing, vibrational analysis, free energy perturbation (FEP) calculations, quantum mechanics/molecular mechanics calculations, stochastic dynamics, and graphing data. 

Solvation is an important parameter that influences macromolecular properties such as solubility, reaction rate equilibria, partition coefficients, enzyme-substrate, and ligand-receptor binding. In free energy calculations, solvent is represented either explicitly or implicitly. The decision of whether to use explicit or implicit solvent models in a given simulation typically depends on the available computer resources. Inclusion of explicit solvent molecules is more realistic than continuum models. 

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