Linear Interaction Energy accessible surface area

Previous studies have shown that there is a correlation between the enthalpy of hydration of alkanes and their accessible surface area [30,31] or related magnitudes. Moreover, relationships between the hydration numbers calculated from discrete simulations for hydrocarbons and both the free energy and enthalpy of hydration of these molecules have also been reported [32] and have been often used to evaluate solvation enthalpies. Analysis of our results, illustrates the existence of a linear relationship between A//n eie and the surface of the van der Waals cavity,. SVw, defined in MST computations for the calculation of the non-electrostatic contributions (Figure 4-1). In contrast, no relationship was found for the electrostatic component of the hydration enthalpy (A//eie data not shown). Clearly, in a first approximation, one can assume that the electrostatic interactions between solute and solvent can be decoupled from the interactions formed between uncharged solutes and solvent molecules. 

For an atom in the enzyme or the substrate to interact with the solvent it must be able to form Van der Waals contact with water molecules. The accessible surface area of an atom is defined as the area on the surface of a sphere, radius R on each point of which the centre of a solvent molecule can be placed in contact with the atom without penetrating any other atoms of the molecule (Fig. 12). R is the sum of the Van der Waals radii of the atom and solvent molecule [27]. There is a linear relationship between the solubility of hydrocarbons and the surface area of the cavity they form in water [28]. It has been estimated that the hydrophobicity of residues in proteins is 100 J/mole/A of accessible surface area [29]. The surface tension of water is 72 dynes/cm so to form a free surface area of water of 1 A costs 435 J/mole/A. The implication is that the free energy of cavity formation in water to receive the hydrophobic group is offset by favourable interactions (dispersion forces) between the solute and water. 

An approximate approach for computing free-energy changes based on linear response (LR) theory is also implemented in BOSS. In this model, the free energy of interaction of a solute with its environment is given as a function of the electrostatic (Coulombic) energy, van der Waals (Lennard-Jones) energy, and solvent-accessible surface area for the solute scaled by empirical parameters, a, p, and y ... 

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